Browse LIF

Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
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 Secreted.
Domain PF01291 LIF / OSM family
Function

LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.

> Gene Ontology
 
Biological Process GO:0001655 urogenital system development
GO:0001656 metanephros development
GO:0001701 in utero embryonic development
GO:0001822 kidney development
GO:0001890 placenta development
GO:0001892 embryonic placenta development
GO:0001893 maternal placenta development
GO:0001933 negative regulation of protein phosphorylation
GO:0001974 blood vessel remodeling
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0002761 regulation of myeloid leukocyte differentiation
GO:0002763 positive regulation of myeloid leukocyte differentiation
GO:0003337 mesenchymal to epithelial transition involved in metanephros morphogenesis
GO:0003338 metanephros morphogenesis
GO:0003339 regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
GO:0006473 protein acetylation
GO:0006475 internal protein amino acid acetylation
GO:0007126 meiotic nuclear division
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0007517 muscle organ development
GO:0007565 female pregnancy
GO:0007566 embryo implantation
GO:0009914 hormone transport
GO:0010001 glial cell differentiation
GO:0010639 negative regulation of organelle organization
GO:0010720 positive regulation of cell development
GO:0010817 regulation of hormone levels
GO:0010948 negative regulation of cell cycle process
GO:0014013 regulation of gliogenesis
GO:0014015 positive regulation of gliogenesis
GO:0016570 histone modification
GO:0016573 histone acetylation
GO:0018105 peptidyl-serine phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018205 peptidyl-lysine modification
GO:0018209 peptidyl-serine modification
GO:0018212 peptidyl-tyrosine modification
GO:0018393 internal peptidyl-lysine acetylation
GO:0018394 peptidyl-lysine acetylation
GO:0019827 stem cell population maintenance
GO:0023061 signal release
GO:0030099 myeloid cell differentiation
GO:0030225 macrophage differentiation
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030856 regulation of epithelial cell differentiation
GO:0030858 positive regulation of epithelial cell differentiation
GO:0031056 regulation of histone modification
GO:0031058 positive regulation of histone modification
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033139 regulation of peptidyl-serine phosphorylation of STAT protein
GO:0033141 positive regulation of peptidyl-serine phosphorylation of STAT protein
GO:0034504 protein localization to nucleus
GO:0035065 regulation of histone acetylation
GO:0035066 positive regulation of histone acetylation
GO:0035850 epithelial cell differentiation involved in kidney development
GO:0040020 regulation of meiotic nuclear division
GO:0042063 gliogenesis
GO:0042326 negative regulation of phosphorylation
GO:0042501 serine phosphorylation of STAT protein
GO:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042508 tyrosine phosphorylation of Stat1 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042510 regulation of tyrosine phosphorylation of Stat1 protein
GO:0042511 positive regulation of tyrosine phosphorylation of Stat1 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:0043409 negative regulation of MAPK cascade
GO:0043410 positive regulation of MAPK cascade
GO:0043543 protein acylation
GO:0043966 histone H3 acetylation
GO:0043974 histone H3-K27 acetylation
GO:0044706 multi-multicellular organism process
GO:0045637 regulation of myeloid cell differentiation
GO:0045639 positive regulation of myeloid cell differentiation
GO:0045649 regulation of macrophage differentiation
GO:0045651 positive regulation of macrophage differentiation
GO:0045685 regulation of glial cell differentiation
GO:0045687 positive regulation of glial cell differentiation
GO:0045786 negative regulation of cell cycle
GO:0045835 negative regulation of meiotic nuclear division
GO:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046697 decidualization
GO:0046879 hormone secretion
GO:0046883 regulation of hormone secretion
GO:0046888 negative regulation of hormone secretion
GO:0048286 lung alveolus development
GO:0048568 embryonic organ development
GO:0048608 reproductive structure development
GO:0048644 muscle organ morphogenesis
GO:0048708 astrocyte differentiation
GO:0048710 regulation of astrocyte differentiation
GO:0048711 positive regulation of astrocyte differentiation
GO:0048771 tissue remodeling
GO:0048861 leukemia inhibitory factor signaling pathway
GO:0048863 stem cell differentiation
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050769 positive regulation of neurogenesis
GO:0051048 negative regulation of secretion
GO:0051051 negative regulation of transport
GO:0051098 regulation of binding
GO:0051101 regulation of DNA binding
GO:0051321 meiotic cell cycle
GO:0051445 regulation of meiotic cell cycle
GO:0051447 negative regulation of meiotic cell cycle
GO:0051783 regulation of nuclear division
GO:0051784 negative regulation of nuclear division
GO:0051962 positive regulation of nervous system development
GO:0060135 maternal process involved in female pregnancy
GO:0060231 mesenchymal to epithelial transition
GO:0060425 lung morphogenesis
GO:0060426 lung vasculature development
GO:0060462 lung lobe development
GO:0060463 lung lobe morphogenesis
GO:0060541 respiratory system development
GO:0060706 cell differentiation involved in embryonic placenta development
GO:0060707 trophoblast giant cell differentiation
GO:0060708 spongiotrophoblast differentiation
GO:0060712 spongiotrophoblast layer development
GO:0060993 kidney morphogenesis
GO:0061005 cell differentiation involved in kidney development
GO:0061326 renal tubule development
GO:0061458 reproductive system development
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070373 negative regulation of ERK1 and ERK2 cascade
GO:0072001 renal system development
GO:0072006 nephron development
GO:0072009 nephron epithelium development
GO:0072028 nephron morphogenesis
GO:0072073 kidney epithelium development
GO:0072077 renal vesicle morphogenesis
GO:0072080 nephron tubule development
GO:0072087 renal vesicle development
GO:0072088 nephron epithelium morphogenesis
GO:0072108 positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
GO:0072160 nephron tubule epithelial cell differentiation
GO:0072170 metanephric tubule development
GO:0072182 regulation of nephron tubule epithelial cell differentiation
GO:0072202 cell differentiation involved in metanephros development
GO:0072207 metanephric epithelium development
GO:0072210 metanephric nephron development
GO:0072215 regulation of metanephros development
GO:0072216 positive regulation of metanephros development
GO:0072234 metanephric nephron tubule development
GO:0072243 metanephric nephron epithelium development
GO:0072257 metanephric nephron tubule epithelial cell differentiation
GO:0072273 metanephric nephron morphogenesis
GO:0072283 metanephric renal vesicle morphogenesis
GO:0072307 regulation of metanephric nephron tubule epithelial cell differentiation
GO:0090183 regulation of kidney development
GO:0090184 positive regulation of kidney development
GO:0097696 STAT cascade
GO:0098727 maintenance of cell number
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1901674 regulation of histone H3-K27 acetylation
GO:1901676 positive regulation of histone H3-K27 acetylation
GO:1901983 regulation of protein acetylation
GO:1901985 positive regulation of protein acetylation
GO:1902105 regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1902275 regulation of chromatin organization
GO:1902532 negative regulation of intracellular signal transduction
GO:1903025 regulation of RNA polymerase II regulatory region sequence-specific DNA binding
GO:1903046 meiotic cell cycle process
GO:1903531 negative regulation of secretion by cell
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1903829 positive regulation of cellular protein localization
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
GO:1905269 positive regulation of chromatin organization
GO:1905330 regulation of morphogenesis of an epithelium
GO:1905332 positive regulation of morphogenesis of an epithelium
GO:2000027 regulation of organ morphogenesis
GO:2000241 regulation of reproductive process
GO:2000242 negative regulation of reproductive process
GO:2000677 regulation of transcription regulatory region DNA binding
GO:2000696 regulation of epithelial cell differentiation involved in kidney development
GO:2000698 positive regulation of epithelial cell differentiation involved in kidney development
GO:2000756 regulation of peptidyl-lysine acetylation
GO:2000758 positive regulation of peptidyl-lysine acetylation
Molecular Function GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding
GO:0001134 transcription factor activity, transcription factor recruiting
GO:0001135 transcription factor activity, RNA polymerase II transcription factor recruiting
GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005146 leukemia inhibitory factor receptor binding
GO:0008083 growth factor activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04630 Jak-STAT signaling pathway
hsa04668 TNF signaling pathway
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-6788467: IL-6-type cytokine receptor ligand interactions
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-449147: Signaling by Interleukins
Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between LIF 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 LIF and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28533357Prostate CarcinomaInhibit immunityTLR9 expression and secretion of LIF by prostate cancer cells stimulates accumulation and activity of polymorphonuclear MDSCs. The PMN-MDSCs from tetracycline-treated RM9-Tlr9ONtumors increased the immunosuppressive activity of the STAT3 transcription factor, thereby more potently inhibiting T cell proliferation.
17848619Ovarian CarcinomaInhibit immunity (T cell function)Ovarian cancer ascites contained high concentrations of LIF and IL-6. Recombinant LIF and IL-6 skew monocyte differentiation into TAM-like cells by enabling monocytes to consume monocyte-colony-stimulating factor (M-CSF). Depletion of LIF, IL-6, and M-CSF in ovarian cancer ascites suppressed TAM-like cell induction.
Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
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 LIF 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 NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
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 LIF in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.9210.228
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.3010.859
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-1.3650.269
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0280.97
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.2210.889
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3520.871
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1820.831
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.7260.604
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11121.4550.273
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.0770.951
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.1530.93
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.8530.000153
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of LIF 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) 27737.407.40.0709
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.407.40.096
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
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
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LIF. 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
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LIF. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LIF.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LIF. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of LIF expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between LIF and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolLIF
Nameleukemia inhibitory factor
Aliases HILDA; differentiation inhibitory activity; differentiation-inducing factor; hepatocyte-stimulating factor I ......
Chromosomal Location22q12.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting LIF collected from DrugBank database.
> Drugs from DrugBank database
 

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