Browse STAT3

Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus Note=Shuttles between the nucleus and the cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3. Identified in a complex with LYN and PAG1.
Domain PF00017 SH2 domain
PF01017 STAT protein
PF02864 STAT protein
PF02865 STAT protein
Function

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:17344214, PubMed:18242580, PubMed:23084476). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:17344214). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity (PubMed:28065600). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity).

> Gene Ontology
 
Biological Process GO:0001654 eye development
GO:0001659 temperature homeostasis
GO:0001754 eye photoreceptor cell differentiation
GO:0001764 neuron migration
GO:0002526 acute inflammatory response
GO:0006090 pyruvate metabolic process
GO:0006091 generation of precursor metabolites and energy
GO:0006096 glycolytic process
GO:0006109 regulation of carbohydrate metabolic process
GO:0006110 regulation of glycolytic process
GO:0006140 regulation of nucleotide metabolic process
GO:0006164 purine nucleotide biosynthetic process
GO:0006165 nucleoside diphosphate phosphorylation
GO:0006417 regulation of translation
GO:0006606 protein import into nucleus
GO:0006732 coenzyme metabolic process
GO:0006733 oxidoreduction coenzyme metabolic process
GO:0006754 ATP biosynthetic process
GO:0006757 ATP generation from ADP
GO:0006839 mitochondrial transport
GO:0006913 nucleocytoplasmic transport
GO:0006953 acute-phase response
GO:0007006 mitochondrial membrane organization
GO:0007219 Notch signaling pathway
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0007423 sensory organ development
GO:0007568 aging
GO:0007631 feeding behavior
GO:0008593 regulation of Notch signaling pathway
GO:0009116 nucleoside metabolic process
GO:0009118 regulation of nucleoside metabolic process
GO:0009119 ribonucleoside metabolic process
GO:0009123 nucleoside monophosphate metabolic process
GO:0009124 nucleoside monophosphate biosynthetic process
GO:0009126 purine nucleoside monophosphate metabolic process
GO:0009127 purine nucleoside monophosphate biosynthetic process
GO:0009132 nucleoside diphosphate metabolic process
GO:0009135 purine nucleoside diphosphate metabolic process
GO:0009141 nucleoside triphosphate metabolic process
GO:0009142 nucleoside triphosphate biosynthetic process
GO:0009144 purine nucleoside triphosphate metabolic process
GO:0009145 purine nucleoside triphosphate biosynthetic process
GO:0009150 purine ribonucleotide metabolic process
GO:0009152 purine ribonucleotide biosynthetic process
GO:0009156 ribonucleoside monophosphate biosynthetic process
GO:0009161 ribonucleoside monophosphate metabolic process
GO:0009163 nucleoside biosynthetic process
GO:0009165 nucleotide biosynthetic process
GO:0009167 purine ribonucleoside monophosphate metabolic process
GO:0009168 purine ribonucleoside monophosphate biosynthetic process
GO:0009179 purine ribonucleoside diphosphate metabolic process
GO:0009185 ribonucleoside diphosphate metabolic process
GO:0009199 ribonucleoside triphosphate metabolic process
GO:0009201 ribonucleoside triphosphate biosynthetic process
GO:0009205 purine ribonucleoside triphosphate metabolic process
GO:0009206 purine ribonucleoside triphosphate biosynthetic process
GO:0009260 ribonucleotide biosynthetic process
GO:0009894 regulation of catabolic process
GO:0009895 negative regulation of catabolic process
GO:0010001 glial cell differentiation
GO:0010310 regulation of hydrogen peroxide metabolic process
GO:0010608 posttranscriptional regulation of gene expression
GO:0010675 regulation of cellular carbohydrate metabolic process
GO:0010677 negative regulation of cellular carbohydrate metabolic process
GO:0010721 negative regulation of cell development
GO:0010727 negative regulation of hydrogen peroxide metabolic process
GO:0010728 regulation of hydrogen peroxide biosynthetic process
GO:0010730 negative regulation of hydrogen peroxide biosynthetic process
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0016052 carbohydrate catabolic process
GO:0016441 posttranscriptional gene silencing
GO:0016458 gene silencing
GO:0017038 protein import
GO:0017148 negative regulation of translation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019362 pyridine nucleotide metabolic process
GO:0019827 stem cell population maintenance
GO:0030336 negative regulation of cell migration
GO:0030522 intracellular receptor signaling pathway
GO:0030808 regulation of nucleotide biosynthetic process
GO:0030810 positive regulation of nucleotide biosynthetic process
GO:0031047 gene silencing by RNA
GO:0032355 response to estradiol
GO:0033210 leptin-mediated signaling pathway
GO:0033500 carbohydrate homeostasis
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034504 protein localization to nucleus
GO:0035019 somatic stem cell population maintenance
GO:0035194 posttranscriptional gene silencing by RNA
GO:0035195 gene silencing by miRNA
GO:0035264 multicellular organism growth
GO:0035278 miRNA mediated inhibition of translation
GO:0040013 negative regulation of locomotion
GO:0040014 regulation of multicellular organism growth
GO:0040029 regulation of gene expression, epigenetic
GO:0040033 negative regulation of translation, ncRNA-mediated
GO:0042063 gliogenesis
GO:0042278 purine nucleoside metabolic process
GO:0042326 negative regulation of phosphorylation
GO:0042451 purine nucleoside biosynthetic process
GO:0042455 ribonucleoside biosynthetic process
GO:0042493 response to drug
GO:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0042593 glucose homeostasis
GO:0042743 hydrogen peroxide metabolic process
GO:0042755 eating behavior
GO:0043434 response to peptide hormone
GO:0043467 regulation of generation of precursor metabolites and energy
GO:0043470 regulation of carbohydrate catabolic process
GO:0044262 cellular carbohydrate metabolic process
GO:0044320 cellular response to leptin stimulus
GO:0044321 response to leptin
GO:0044723 single-organism carbohydrate metabolic process
GO:0044724 single-organism carbohydrate catabolic process
GO:0044744 protein targeting to nucleus
GO:0045471 response to ethanol
GO:0045747 positive regulation of Notch signaling pathway
GO:0045820 negative regulation of glycolytic process
GO:0045862 positive regulation of proteolysis
GO:0045912 negative regulation of carbohydrate metabolic process
GO:0045974 regulation of translation, ncRNA-mediated
GO:0045978 negative regulation of nucleoside metabolic process
GO:0045979 positive regulation of nucleoside metabolic process
GO:0045980 negative regulation of nucleotide metabolic process
GO:0045981 positive regulation of nucleotide metabolic process
GO:0046031 ADP metabolic process
GO:0046034 ATP metabolic process
GO:0046128 purine ribonucleoside metabolic process
GO:0046129 purine ribonucleoside biosynthetic process
GO:0046390 ribose phosphate biosynthetic process
GO:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046496 nicotinamide nucleotide metabolic process
GO:0046530 photoreceptor cell differentiation
GO:0046902 regulation of mitochondrial membrane permeability
GO:0046939 nucleotide phosphorylation
GO:0048592 eye morphogenesis
GO:0048638 regulation of developmental growth
GO:0048708 astrocyte differentiation
GO:0048863 stem cell differentiation
GO:0048871 multicellular organismal homeostasis
GO:0050665 hydrogen peroxide biosynthetic process
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050768 negative regulation of neurogenesis
GO:0050795 regulation of behavior
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051186 cofactor metabolic process
GO:0051193 regulation of cofactor metabolic process
GO:0051195 negative regulation of cofactor metabolic process
GO:0051196 regulation of coenzyme metabolic process
GO:0051198 negative regulation of coenzyme metabolic process
GO:0051271 negative regulation of cellular component movement
GO:0051961 negative regulation of nervous system development
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0060019 radial glial cell differentiation
GO:0060147 regulation of posttranscriptional gene silencing
GO:0060148 positive regulation of posttranscriptional gene silencing
GO:0060259 regulation of feeding behavior
GO:0060396 growth hormone receptor signaling pathway
GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway
GO:0060416 response to growth hormone
GO:0060964 regulation of gene silencing by miRNA
GO:0060966 regulation of gene silencing by RNA
GO:0060968 regulation of gene silencing
GO:0061614 pri-miRNA transcription from RNA polymerase II promoter
GO:0070102 interleukin-6-mediated signaling pathway
GO:0070741 response to interleukin-6
GO:0070997 neuron death
GO:0071354 cellular response to interleukin-6
GO:0071375 cellular response to peptide hormone stimulus
GO:0071378 cellular response to growth hormone stimulus
GO:0071407 cellular response to organic cyclic compound
GO:0071417 cellular response to organonitrogen compound
GO:0072522 purine-containing compound biosynthetic process
GO:0072524 pyridine-containing compound metabolic process
GO:0072593 reactive oxygen species metabolic process
GO:0090559 regulation of membrane permeability
GO:0090596 sensory organ morphogenesis
GO:0097009 energy homeostasis
GO:0097305 response to alcohol
GO:0097696 STAT cascade
GO:0098727 maintenance of cell number
GO:1900371 regulation of purine nucleotide biosynthetic process
GO:1900373 positive regulation of purine nucleotide biosynthetic process
GO:1900542 regulation of purine nucleotide metabolic process
GO:1900543 negative regulation of purine nucleotide metabolic process
GO:1900544 positive regulation of purine nucleotide metabolic process
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901293 nucleoside phosphate biosynthetic process
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1901657 glycosyl compound metabolic process
GO:1901659 glycosyl compound biosynthetic process
GO:1902593 single-organism nuclear import
GO:1902728 positive regulation of growth factor dependent skeletal muscle satellite cell proliferation
GO:1902893 regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1903409 reactive oxygen species biosynthetic process
GO:1903426 regulation of reactive oxygen species biosynthetic process
GO:1903427 negative regulation of reactive oxygen species biosynthetic process
GO:1903578 regulation of ATP metabolic process
GO:1903579 negative regulation of ATP metabolic process
GO:1903580 positive regulation of ATP metabolic process
GO:1904683 regulation of metalloendopeptidase activity
GO:1904685 positive regulation of metalloendopeptidase activity
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
GO:1905048 regulation of metallopeptidase activity
GO:1905050 positive regulation of metallopeptidase activity
GO:2000146 negative regulation of cell motility
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000378 negative regulation of reactive oxygen species metabolic process
GO:2000637 positive regulation of gene silencing by miRNA
GO:2000736 regulation of stem cell differentiation
GO:2000737 negative regulation of stem cell differentiation
GO:2001169 regulation of ATP biosynthetic process
GO:2001171 positive regulation of ATP biosynthetic process
GO:2001222 regulation of neuron migration
GO:2001223 negative regulation of neuron migration
Molecular Function GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001085 RNA polymerase II transcription factor binding
GO:0001103 RNA polymerase II repressing transcription factor binding
GO:0001159 core promoter proximal region DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0001664 G-protein coupled receptor binding
GO:0003682 chromatin binding
GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
GO:0005126 cytokine receptor binding
GO:0008134 transcription factor binding
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
GO:0031490 chromatin DNA binding
GO:0031730 CCR5 chemokine receptor binding
GO:0035257 nuclear hormone receptor binding
GO:0035258 steroid hormone receptor binding
GO:0035259 glucocorticoid receptor binding
GO:0042379 chemokine receptor binding
GO:0043566 structure-specific DNA binding
GO:0048020 CCR chemokine receptor binding
GO:0051427 hormone receptor binding
GO:0070491 repressing transcription factor binding
GO:0098531 transcription factor activity, direct ligand regulated sequence-specific DNA binding
Cellular Component GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0005667 transcription factor complex
GO:0005743 mitochondrial inner membrane
GO:0044454 nuclear chromosome part
GO:0044798 nuclear transcription factor complex
GO:0090575 RNA polymerase II transcription factor complex
> KEGG and Reactome Pathway
 
KEGG hsa04062 Chemokine signaling pathway
hsa04066 HIF-1 signaling pathway
hsa04068 FoxO signaling pathway
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04630 Jak-STAT signaling pathway
hsa04917 Prolactin signaling pathway
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-390471: Association of TriC/CCT with target proteins during biosynthesis
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-390466: Chaperonin-mediated protein folding
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-1839124: FGFR1 mutant receptor activation
R-HSA-982772: Growth hormone receptor signaling
R-HSA-168256: Immune System
R-HSA-6783783: Interleukin-10 signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-6783589: Interleukin-6 family signaling
R-HSA-1059683: Interleukin-6 signaling
R-HSA-8875791: MET activates STAT3
R-HSA-392499: Metabolism of proteins
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-2892247: POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-8849474: PTK6 Activates STAT3
R-HSA-391251: Protein folding
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
R-HSA-162582: Signal Transduction
R-HSA-1226099: Signaling by FGFR in disease
R-HSA-5655302: Signaling by FGFR1 in disease
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-6806834: Signaling by MET
R-HSA-186797: Signaling by PDGF
R-HSA-8848021: Signaling by PTK6
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-1839117: Signaling by cytosolic FGFR1 fusion mutants
R-HSA-166520: Signalling by NGF
R-HSA-198745: Signalling to STAT3
R-HSA-452723: Transcriptional regulation of pluripotent stem cells
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between STAT3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between STAT3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28276425Breast CarcinomaInhibit immunity; Resistant to immunotherapyHerein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells. Impaired Y239/Y240-ShcA phosphorylation selectively reduces STAT3 activation in breast tumours, profoundly sensitizing them to immune checkpoint inhibitors and tumour vaccines. Finally, the ability of diminished tyrosine kinase signalling to initiate STAT1-driven immune surveillance can be overcome by compensatory STAT3 hyperactivation in breast tumours.
26719528Breast CarcinomaInhibit immunitySTAT3 Establishes an Immunosuppressive Microenvironment during the Early Stages of Breast Carcinogenesis to Promote Tumor Growth and Metastasis.
27001312GliomaInhibit immunity (T cell function)Mechanistically, glioma initiating CD133(+) cells and Mφs/microglia cointeraction activated expression of B7-H4 via IL6 and IL10 in both tumor cells and microenvironment supporting cells. IL6-activated STAT3 bound to the promoter of B7-H4 gene and enhanced B7-H4 expression. Furthermore, CD133(+) cells mediated immunosuppression through B7-H4 expression on Mφs/microglia by silencing of B7-H4 expression on these cells, which led to increased microenvironment T-cell function and tumor regression in the xenograft glioma mouse model.
27216177Hepatocellular CarcinomaInhibit immunity (T cell function)In a murine liver tumor model, we found that FAP(+)CAFs were a major source of CCL2 and that fibroblastic STAT3-CCL2 signaling in this setting promoted tumor growth by enhancing recruitment of myeloid-derived suppressor cells (MDSC).
27197152Breast CarcinomaInhibit immunity (T cell function)We suggest that targeting STAT3-NOTCH cross-talk between MDSC and CSC could offer a unique locus to improve cancer treatment, by coordinately targeting a coupled mechanism that enables cancer stemness and immune escape.
26239999Renal Cell CarcinomaInhibit immunity (T cell function)Furthermore, mechanistic investigation revealed that Sunitinib treatment reprograms tumor-associated macrophages toward classically activated or "M1" polarization upon GITR stimulation and consequently mounts an antitumor CD8(+) T and NK cell response via inhibiting STAT3 activity.
26208907Colorectal CarcinomaInhibit immunity (infiltration)As compared with Stat3-sufficient control tumors, Stat3(-/-) cancer cells exhibited an increased infiltration by dendritic cells and cytotoxic T lymphocytes after chemotherapy.
26025380Melanoma; Lung CarcinomaInhibit immunity (T cell function)Together, our study reveals a negative regulation by STAT3 signaling in T cells on cross-talk between myeloid cells and T cells through IFNγ/CXCR3/CXCL10, which is important for CD8(+) T cells homing to tumors.
25967142Prostate CarcinomaInhibit immunity (T cell function)TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients
25597412Non-Small Cell Lung CarcinomaInhibit immunity (T cell function)Our discoveries suggest that the miR-197/CKS1B/STAT3-mediated network can drive tumor PD-L1 expression as a biomarker of this cascade, and miR-197 replacement therapy may be a potential treatment strategy for chemoresistant NSCLC.
25393367Hepatocellular CarcinomaInhibit immunity (NK cell function)SAHA downregulated the miR-17-92 cluster by abolishing tyrosine phosphorylation of STAT3 and decreased MCM7 transcription through localised histone deacetylation. SAHA upregulates the transcription of MICA/B by promoting MICA-associated histone acetylation while suppressing the MICA/B-targeting miRNAs miR-20a, miR-93 and miR-106b. In addition to the immediate effects on the tumour cell growth, HDACi upregulates the expression of MHC class I-related chain molecules A and B (MICA and MICB), resulting in an enhanced susceptibility of tumour cells to natural killer cell-mediated lysis.
22728650LymphomaInhibit immunity (T cell function)Here, we show that genetic or pharmacologic disruption of Stat3 in malignant B cells augments their immunogenicity leading to better activation of antigen-specific CD4(+) T cells and restoration of responsiveness of tolerized T cells.
22588558Nasopharyngeal CarcinomaInhibit immunityIn epithelial cells, LMP1 up-regulated HLA class I APM. This effect could be counteracted by c-Myc, which itself was up-regulated by LMP1 apparently through IL6 induction and Jak3/STAT3 activation. These findings raise the possibility that c-Myc activation in nasopharyngeal carcinoma (NPC) might antagonise the effect of LMP1 on HLA class I expression thus contributing to immune escape of tumour cells.
22529296MelanomaInhibit immunity (T cell function)These data suggest a critical role for tumor-expressed iNOS in the recruitment and induction of functional MDSC by modulation of tumor VEGF secretion and upregulation of STAT3 and ROS in MDSC.
29379494Chronic Lymphocytic LeukemiaInhibit immunityThe CXCR4-STAT3-IL-10 Pathway Controls the Immunoregulatory Function of Chronic Lymphocytic Leukemia and Is Modulated by Lenalidomide. Knockdown of STAT3 significantly impaired the ability of CLL cells to produce IL-10.
27678219MelanomaInhibit immunityCollectively, our data reveal a previously unrecognized STAT3-mediated immunosuppressive mechanism in DCs and indicate that DC-intrinsic ID2 promotes tumor immunity by modulating tumor-associated CD4(+) T cell responses. Thus, inhibiting STAT3 or overexpressing ID2 selectively in DCs may improve the efficiency of DC vaccines in cancer therapy.
29379494Chronic Lymphocytic LeukemiaInhibit immunity (T cell function); immunotherapy targetHere, we show that the CXC chemokine ligand 12 (CXCL12)-CXCR4-STAT3 axis regulates IL-10 production by CLL cells and their ability to suppress T-cell effector function through an IL-10 mediated mechanism. We conclude that the capacity of CLL cells to produce IL-10 is mediated by the CXCL12-CXCR4-STAT3 pathway and likely contributes to immunodeficiency in patients.
24681959Breast CarcinomaInhibit immunity; immunotherapy targetDrug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer. Signal transducer and activator of transcription (STAT) 3 regulates many cardinal features of cancer including cancer cell growth, apoptosis resistance, DNA damage response, metastasis, immune escape, tumor angiogenesis, the Warburg effect and oncogene addiction and has been validated as a drug target for cancer therapy.
24651526Colon carcinomaImmunotherapy targetEmbelin reduces colitis-associated tumorigenesis through limiting IL-6/STAT3 signaling. In addition to inhibiting proliferation of tumor epithelial cells, embelin suppressed colonic IL-6 expression and secretion, and subsequently STAT3 activation in vivo.
18392040MelanomaInhibit immunity (T and NK cell function); immunotherapy targetSynergistic antitumor effects of CpG oligodeoxynucleotide and STAT3 inhibitory agent JSI-124 in a mouse melanoma tumor model. Correlating with these findings, the combination therapy resulted in significantly higher intra-tumoral levels of several proinflammatory, TH1-related cytokines (including IL-12, IFN-gamma, TNF-alpha and IL-2), increases in intra-tumoral CD8+ and CD4+ T cells expressing activation/memory markers and NK cells and increases in activated DCs in the tumors and regional lymph nodes (LNs). Concomitantly, the combination therapy led to a significantly decreased level of immunosuppression, as evidenced by lower intra-tumoral level of VEGF and TGF-beta, and decreased number of CD4+CD25+Foxp3+ regulatory T cells in the regional LNs.
19306372GilomaInhibit immunityFinally, the effect of Stat3 inhibition on tumor growth was assessed in intracranial GL261 gliomas. GL261-CM increased Stat3 activity in N9 cells in vitro and resulted in overexpression of IL-10 and IL-6, and downregulation of IL1-beta, a pro-inflammatory cytokine. Inhibition of Stat3 by CPA-7 or siRNA reversed glioma-induced cytokine expression profile in N9 cells. Furthermore, inactivation of Stat3 in intracranial GL261 tumors by siRNA resulted in MG/MP activation and tumor growth inhibition. Glioma-induced MG and MP suppression may be mediated thorough Stat3. Inhibition of Stat3 function in tumor MG/MP may result in their activation and can potentially be used as an adjunct immunotherapy approach for gliomas.
19258507MelanomaInhibit immunity (T cell function)CpG directly activates Stat3 within minutes through TLR9. Ablating Stat3 in hematopoietic cells results in rapid activation of innate immunity by CpG, with enhanced production of IFN-gamma, tumor necrosis factor-alpha, IL-12, and activation of macrophages, neutrophils, and natural killer cells marked with Stat1 activation. Innate immune responses induced by CpG in mice with a Stat3-ablated hematopoietic system cause potent antitumor effects, leading to eradication of large (>1 cm) B16 melanoma tumors within 72 h. Our results further suggest that targeting Stat3 can drastically improve CpG-based immunotherapeutic approaches.
28533357Prostate CarcinomaInhibit immunity (T cell function)The PMN-MDSCs from tetracycline-treated RM9-Tlr9ONtumors increased the immunosuppressive activity of the STAT3 transcription factor, thereby more potently inhibiting T cell proliferation.
28497804GliomaInhibit immunity (T cell function); essential for immunotherapyHowever, some preclinical trial data suggest that addition of immunomodulatory reagents such as immune checkpoint inhibitors, transforming growth factor-β inhibitors, signal transducer and activator of transcription 3 inhibitors, or modifiers of tryptophan metabolism could augment the therapeutic activity of vaccination and overcome glioma-associated immunosuppression.
28478231Non-Small Cell Lung CarcinomaInhibit immunity (T cell function)Radiotherapy may up-regulate PD-L1 expression through the phosphoinositide 3-kinase/AKT and signal transducer and activator of transcription 3 pathways.
23514705Pancreatic CarcinomaInhibit immunity (T cell function)Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner.
23440412Breast CarcinomaInhibit immunity (T cell function)The proportion of MDSCs with the phenotype of CD45(+)CD13(+)CD33(+)CD14(-)CD15(-) significantly increased in primary cancer tissues and patients' peripheral blood. IDO expression was significantly upregulated in MDSCs isolated from fresh breast cancer tissues (fresh MDSCs [fMDSCs]), which correlated with increased infiltration of Foxp3(+) regulatory T cells in tumors and lymph node metastasis in patients. IDO expression was upregulated in induced MDSCs, which required phosphorylation of STAT3, but not STAT1.
21257710Colorectal CarcinomaInhibit immunityIn this study, we investigated the role of STAT3 in suppressing NK cell-mediated immunosurveillance. Using a colorectal cancer cell line (HT29) that can poorly activate NK, we neutralized STAT3 with pharmacologic inhibitors or siRNA and found that this led to an increase in NK degranulation and IFN-γ production in a TGF-β1-independent manner.
21118964Renal Cell Carcinoma; MelanomaInhibit immunity (T cell function)Sunitinib inhibited Stat3 in dendritic cells and T cells and reduced conversion of transferred FoxP3(-) T cells to tumor-associated regulatory T cells while increasing transferred CD8(+) T-cell infiltration and activation at the tumor site, leading to inhibition of primary tumor growth.
27593937Hepatocellular CarcinomaInhibit immunity (T cell function); immunotherapy targetTumor-associated fibroblasts (TAFs) attracted monocytes by the stromal cell-derived factor (SDF)-1a/CXCR4 pathway and induced their differentiation into MDSCs through interleukin (IL)-6-mediated STAT3 activation. These data also suggest an important role for STAT3 activation in TAF-mediated MDSC generation and MDSC-mediated immune suppression. Consequently, methods in which immunotherapy is combined with IL-6, SDF-1a or STAT3 inhibition may offer an improved option to eliminate suppressive CD11b+ myeloid cells in HCC patients.
23633486MelanomaInhibit immunity (T cell function)Further, this induction is largely dependent on production of cyclooxygenase-2 (COX-2) because its inhibition in these MDSC-like cells limits their ability to suppress T-cell function. We confirmed our findings with CD14(+) cells isolated from patients with advanced stage melanoma, which inhibited autologous T cells in a manner relying up prostaglandin E2 (PGE2), STAT-3, and superoxide.
18250414GliomaInhibit immunity; immunotherapy targetThese data suggest that systemic inhibition of STAT3 signaling can reverse the suppressive immunological environment of intracranial tumor bearing mice both systemically and locally, thereby promoting the efficacy of adoptive transfer therapy with Tc1.
19088040GliomaInhibit immunity (T cell function)p-STAT3 expression was associated with the population of tumor-infiltrating immune cells but not with that of T regulatory cells.
17942891GlioblastomaInhibit immunity (T cell function)Signal transducers and activators of transcription 3 (STAT3) has recently emerged as a potential target for effective immunotherapy, and in this study, we describe a novel small molecule inhibitor of STAT3 that can penetrate the central nervous system (CNS) in mice and in physiologically relevant doses in vitro and reverse tolerance in immune cells isolated from glioblastoma multiforme (GBM) patients. Specifically, it induces the expression of costimulatory molecules on peripheral macrophages and tumor-infiltrating microglia, stimulates the production of the immune-stimulatory cytokines interleukin 2 (IL-2), IL-4, IL-12, and IL-15, and induces proliferation of effector T cells from GBM patients that are refractory to CD3 stimulation.
24963846melanomaInhibit immunityMMP-9 is upregulated in a panel of rounded-amoeboid compared with elongated-mesenchymal melanoma cell lines and its levels are controlled by ROCK-JAK-STAT3 signalling.
24912675Hepatocellular CarcinomaInhibit immunity (T cell function); resistant to immunotherapysuppression abolished the IL-6-mediated effects in normal Chang cells, but it did not recover the TM4SF5-dependent FAK activity that was inhibited by IL-6 treatment in cancerous SNU761-TM4SF5 cells.
29636826lung carcinomaInhibit immunityWe have actively worked on the role of STAT3, a transcriptional factor that causes innate resistance to targeted therapies in oncogene-addicted tumors.
29632728glioblastomaInhibit immunityMass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch.
29596910Recurrent Non-Small Cell Lung CarcinomaInhibit immunity (T cell function)Oncogene-driven expression of PD-L2 in NSCLC cells was inhibited by knockdown of the transcription factors signal transducer and activator of transcription 3 (STAT3) or c-FOS.
27890932Chronic lymphocytic leukemiaInhibit immunityA functional signal transducer and activator of transcription 3 (STAT3) binding site in CLL-VMR2 was confirmed by proximity ligation and luciferase assays, whereas inhibition of SYK-mediated STAT3 activation resulted in suppression of IL10.
27863995MelanomaInhibit immunityTo effectively treat this aggressive tumor, a multi-target receptor tyrosine kinase inhibitor, sunitinib base, was efficiently encapsulated into a targeted polymeric micelle nano-delivery system (SUNb-PM), working in a synergistic manner with vaccine therapy in an advanced mouse melanoma model. Inhibition of the Stat3 and AKT signaling pathways by SUNb-PM may induce tumor cell apoptosis or decrease tumor immune evasion.
24068730MedulloblastomaInhibit immunityFor example, myeloid derived suppressor cells (MDSCs) are thought to promote tumor growth by several mechanisms, including the suppression of T cell activity. It has been suggested that STAT3 activation in myeloid cells modulates multiple aspects of MDSC physiology, including their expansion and activity. In fully developed tumors, pSTAT3 was found in the majority of these cells. Conditional STAT3 gene disruption in myeloid cells resulted in an enhanced proinflammatory phenotype of macrophages in Smo* mice.
23958949LymphomaInhibit immunityFirst, DD modulated DCs toward tolerance by downregulating costimulatory receptors such as CD83 and CD25 while upregulating tolerance-associated proteins/pathways including Stat-3, β-catenin, and class II transactivator-dependent antigen presentation.
21527558MelanomaInhibit immunity (T cell function)Vaccine efficacy could be rescued if tumor-bearing mice were treated initially with Salmonella encoding a short hairpin RNA (shRNA) targeting the tolerogenic molecule STAT3 (YS1646-shSTAT3). In vaccinated mice, silencing STAT3 increased the proliferation and granzyme B levels of intratumoral CD4(+) and CD8(+) T cells. The combined strategy also increased apoptosis in tumors of treated mice, enhancing tumor-specific killing of tumor targets.
21310826Colorectal CancinomaInhibit immunitySTAT3 is a transcription factor that is constitutively activated in some cancers. It seems to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. p-STAT3 overexpression was associated with significantly higher colorectal cancer-specific mortality [log-rank P = 0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative): 1.85, 95% CI: 1.30-2.63, P(trend) = 0.0005; multivariate HR: 1.61, 95% CI: 1.11-2.34, P(trend) = 0.015]. p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate OR: 3.23; 95% CI: 1.89-5.53, P < 0.0001).
20053772GlioblastomaInhibit immunityRecent studies have found that the activated form of signal transducer and activator of transcription 3 (STAT3) is a key mediator in GBM immunosuppression. The STAT3 pathway is constitutively active in these clones and the immunosuppressive properties were markedly diminished when the STAT3 pathway was blocked in the cancer-initiating cells. These findings indicate that cancer-initiating cells contribute to the immune evasion of GBM and that blockade of the STAT3 pathway has therapeutic potential.
29215754Head and Neck Squamous Cell CarcinomaInhibit immunityInhibition of JAK2/STAT3 reduces tumor-induced angiogenesis and myeloid-derived suppressor cells in head and neck cancer. Moreover, in HNSCC transgenic mouse model, inhibiting JAK2/STAT3 not only suppressed angiogenesis but also reduced MDSCs in the tumor microenvironment through suppressing VEGFA and CK2. Our findings demonstrated the close relationship between angiogenesis and MDSCs in HNSCC, and inhibition of JAK2/STAT3 could reduce tumor-induced angiogenesis and decrease MDSCs.
18676737GlioblastomaInhibit immunityAberrant activation of STAT proteins, particularly STAT-3, is implicated in the pathogenesis of many cancers, including GBM, by promoting cell cycle progression, stimulating angiogenesis, and impairing tumor immune surveillance. Conversely, PIAS3 overexpression inhibited STAT-3 transcriptional activity, expression of STAT-3-regulated genes, and cell proliferation.
15986140MelanomaInhibit immunitySTAT3 participates in the regulation of tumor immune evasion by inhibiting expression of proinflammatory mediators while promoting expression of immune-suppressing factors, which in turn activates STAT3 signaling in dendritic cells leading to immune tolerance.
29438108Lung Carcinoma; Breast CarcinomaInhibit immunity (infiltration)Furthermore, using knock-in transgenic mouse models for lung and breast cancers, we establish the host-specific tumor-extrinsic functions of STAT3-enhancing germline variants in impeding the tumor infiltration of CD8 T cells. Thus, STAT3-enhancing germline receptor variants contribute to immune evasion through their pleiotropic functions in immune cells.
28108629Lung CarcinomaInhibit immunityWe found that antitumor type 1 CD4+T-helper (Th1) cells and CD8+T cells were directly counter balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8+T cells, enhancement of cytotoxicity toward CD4+and CD8+T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DC), and polarization of macrophages toward the M2 phenotype.
24177177Prostate CarcinomaInhibit immunityIn human prostate tumor tissues, elevated cancer stem-like cell markers coincide with those cells exhibiting high STAT3 activity and low AR expression. AR downregulation-induced STAT3 activation is mediated through increased interleukin (IL)-6 expression. Treating mice with soluble IL-6 receptor fusion protein or silencing STAT3 in tumor cells significantly reduced prostate tumor growth and CSCs.
24169824Acute Myeloid LeukemiaInhibit immunityLeukemia cell-targeted STAT3 silencing and TLR9 triggering generate systemic antitumor immunity. CpG-Stat3 siRNA has direct immunogenic effect on AML cells in vivo upregulating major histocompatibility complex class-II, costimulatory and proinflammatory mediators, such as interleukin-12, while downregulating coinhibitory PD-L1 molecule. Systemic injections of CpG-Stat3 siRNA generate potent tumor antigen-specific immune responses, increase the ratio of tumor-infiltrating CD8(+) T cells to regulatory T cells in various organs, and result in CD8(+) T-cell-dependent regression of leukemia.
24131405Breast CarcinomaInhibit immunitySystemic delivery of PCPS/STAT3 siRNA in murine model of MDA-MB-231 breast cancer enriched particles in tumor tissues and reduced STAT3 expression in cancer cells, causing significant reduction of cancer stem cells in the residual tumor tissue.
24107450Hepatocellular CarcinomaInhibit immunityTargeting blockage of STAT3 in hepatocellular carcinoma cells augments NK cell functions via reverse hepatocellular carcinoma-induced immune suppression. In the case of STAT3-blocked hepatocellular carcinoma cells, NKG2D ligands were upregulated, which promoted recognition by NK cells. Indeed, the cytotoxicity of NK cells treated with supernatant from STAT3-blocked hepatocellular carcinoma cells was augmented, with a concomitant elevation of molecules associated with NK cytolysis.
22753933Breast CarcinomaInhibit immunityTherapeutic immunization with Stat3Y705F-breast cancer cells inhibited tumor growth, promoted tumor cell differentiation, and decreased metastasis. Furthermore, inhibition of Stat3 activation in breast cancer cells induced cellular senescence, contributing to their immunogenic phenotype. In this work, we provide preclinical proof of concept that ablating Stat3 signaling in breast cancer cells results in an effective immunotherapy against breast cancer growth and metastasis.
22745305Diffuse Large B-Cell LymphomaInhibit immunitySTAT3 plays a crucial role in promoting progression of human cancers, including several types of B-cell lymphoma.
22203730Gastric CarcinomaInhibit immunityInhibition of STAT3 signaling pathway by nitidine chloride suppressed the angiogenesis and growth of human gastric cancer. Furthermore, nitidine chloride suppressed the constitutively activated STAT3 protein, its DNA-binding activity, and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF in human gastric cancer cells.
21632716Colon AdenocarcinomaInhibit immunityIntratumoral administration of STAT3-depleted DCs significantly inhibited MC38 tumor growth of both injected and nontreated remote tumors. STAT3-depleted human DCs with adenoviral STAT3 short hairpin RNA were also capable of producing more cytokines with TLR stimulation and more resistant to cancer-derived factors, and they induced tumor Ag-specific T cells more efficiently than control DCs.
20682796Head and Neck Squamous Cell CarcinomaInhibit immunity; Candidate for immunotherapy targetSTAT3 inhibition in multiple primary and established human squamous carcinoma lines resulted in enhanced expression and secretion of both proinflammatory cytokines and chemokines. Moreover, supernatants from STAT3-silenced tumor cells were able to stimulate the migratory behavior of lymphocytes from human peripheral blood in vitro. These results show the importance of STAT3 activation in regulating the immunomodulatory mediators by human tumors and further validate STAT3 as a promising target for therapeutic intervention.
20667896GlioblastomaInhibit immunityThe role of the signal transducer and activator of transcription 3 (STAT3) in mediating innate immune suppression was evaluated in the context of the functional assays. The inhibition of phagocytosis and the secretion of IL-10 were reversed when the STAT3 pathway was blocked in the gCSCs. The gCSCs modulate innate immunity in glioblastoma by inducing immunosuppressive MΦs/microglia, and this capacity can be reversed by inhibiting phosphorylated STAT3.
20388845Metastatic MelanomaInhibit immunity; Resistant to immunotherapyInhibition of p-STAT3 enhances IFN-alpha efficacy against metastatic melanoma in a murine model. Activation of the signal transducer and activator of transcription 3 (STAT3) has been identified as a key mediator that drives the fundamental components of melanoma malignancy, including immune suppression in melanoma patients. The immune modulatory effects of STAT3 blockade can enhance the therapeutic efficacy of IFN-alpha immunotherapy by enhancing both innate and adaptive cytotoxic T-cell activities.
29702007Breast CarcinomaInhibit immunityDual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells. We found that individual inhibition of STAT1 and STAT3 activation partially downregulated PD-L1, while combined inhibition completely downregulated PD-L1 expression.
25238096lung carcinoma; melanoma; colon carcinomaInhibit immunity (T cell function)Transcription factors CCAAT/enhancer binding protein b (C/EBPb) and phosphorylated signal transducer of activator of transcription 3 (phospho-STAT3) centrally regulate MDSC function and expansion
25085111lung carcinomaInhibit immunityCD80 loss on HBC was dependent on CD11b MC CD11b expression and STAT3 activity.
25063873Breast CarcinomaInhibit immunityThese results demonstrate a STAT3/NF-κB/IDO pathway in breast cancer-derived MDSCs, which provides insight into understanding immunosuppressive mechanisms of MDSCs in breast cancer. We have identified a poorly differentiated MDSC subset in breast cancer-suppressing T cell function through STAT3-dependent IDO upregulation
21898502Hepatocellular CarcinomaInhibit immunityIn addition, sunitinib treatment of tumor-bearing mice was associated with suppression of STAT3 and a block in T-cell tolerance. These findings indicate that sunitinib inhibits HCC tumor growth directly through the STAT3 pathway and prevents tumor antigen-specific CD8(+) T-cell tolerance, thus defining a synergistic chemoimmunotherapeutic approach for HCC.
16917008Multiple myeloma(IgA, IgD, IgE, IgM, IgG)Inhibit immunityThese abnormalities may be attributed to elevated production of autocrine cytokines such as IL-6, activated p38 and STAT3, and inhibited MEK/ERK signaling pathways in the progenitor cells. Treatment with neutralizing IL-6-specific antibody and, more importantly, p38 inhibitor, or both, could correct these abnormalities. Treating patient-derived cells with these agents not only significantly increased cell yield but also produced MoDCs that were as functional as their normal counterparts.
16801397MelanomaInhibit immunityThese results indicate that the MAPK signal, along with the STAT3 signal, is essential for immune evasion by human melanomas that have constitutively active MAPK signaling and is a potential molecular target for overcoming melanoma cell evasion of the immune system.
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of STAT3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.08; FDR: 0.04630 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of STAT3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.3050.272
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0690.978
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.4780.797
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1080.735
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3030.911
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6280.859
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2330.609
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.360.862
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0770.974
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.0770.966
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4040.881
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0990.12
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of STAT3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.212.59.70.602
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59022.2-22.20.505
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47500500.109
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of STAT3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of STAT3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by STAT3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of STAT3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of STAT3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between STAT3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSTAT3
Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Aliases APRF; ADMIO; HIES; DNA-binding protein APRF; acute-phase response factor; Signal transducer and activator of ......
Chromosomal Location17q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting STAT3 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting STAT3.
ID Name Drug Type Targets #Targets
DB05959ENMD-1198Small MoleculeHIF1A, STAT3, TNFRSF11A3