Browse MSLN

Summary
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
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 Cell membrane; Lipid-anchor, GPI-anchor. Golgi apparatus.; SUBCELLULAR LOCATION: Megakaryocyte-potentiating factor: Secreted.; SUBCELLULAR LOCATION: Isoform 3: Secreted.
Domain PF06060 Pre-pro-megakaryocyte potentiating factor precursor (Mesothelin)
Function

Membrane-anchored forms may play a role in cellular adhesion.; FUNCTION: Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.

> Gene Ontology
 
Biological Process GO:0007160 cell-matrix adhesion
GO:0031016 pancreas development
GO:0031589 cell-substrate adhesion
Molecular Function -
Cellular Component GO:0031225 anchored component of membrane
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-392499: Metabolism of proteins
R-HSA-163125: Post-translational modification
R-HSA-597592: Post-translational protein modification
Summary
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MSLN 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 MSLN and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
18281514Pancreatic CarcinomaInhibit immunity (T cell function); immunotherapy targetWe have shown that mesothelin expression was higher in human pancreatic cancer cells than in human pancreatic duct epithelial cells, and mesothelin mRNA was substantially overexpressed in 18 of 21 (86%) clinical pancreatic adenocarcinoma specimens when compared with the surrounding normal tissues. The increases in mesothelin-specific antibodies and CTL activity and the decrease in regulatory T cells correlated with reduced tumor progression and prolonged survival.
22418702Triple-negative breast carcinomaPromote immunity (T cell function); essential for immunotherapyMSLN is expressed in majority of triple negative breast carcinoma, while very rare in positive breast cancer. Application of CAR T modified to express MSLN-specific chimeric antibody receptor exert higher anti-tumor cytotoxicity than non-transduced T cells, suggesting that MSLN is a novel immunotherapy target. Therefore, we screened 99 primary breast cancer samples by immunohistochemistry analysis using formalin-fixed paraffin-embedded archival tumor tissues and confirmed that mesothelin was overexpressed in the majority of TNBC (67 %) but only rarely in <5 % ER(+) or Her2-neu(+) breast cancer, respectively. A significantly higher anti-tumor cytotoxicity by mesoCAR T cells was observed (31.7 vs. 8.7 %, p < 0.001). Our results suggest that mesothelin has promise as a novel immunotherapy target for TNBC for which effective targeted therapy is lacking to date.
23183537Cervical carcinomaInhibit immunityThe tumor-homing module is comprised of a single-chain variable fragment (scFv) that specifically binds to mesothelin (Meso), which is commonly overexpressed in human cancers, including ovarian tumors. We show that our therapeutic protein specifically loaded antigenic epitope onto the surface of mesothelin-expressing tumor cells, rendering tumors susceptible to antigen-specific cytotoxic CD8(+) T lymphocytes (CTL)-mediated killing in vitro and in vivo. Our findings have important implications for bypassing immune tolerance to enhance cancer immunotherapy.
29596890ovarian carcinoma; Pancreatic ductal adenocarcinoma; mesotheliomaPromote immunityThe results indicate that an MSLN-specific DNA vaccine combined with immuno-modulators may be an effective immunotherapeutic strategy to control MSLN-expressing tumors including ovarian and pancreastic cancers, and malignant mesothelioma.
27863199Malignant Mesothelioma; Pancreatic Adenocarcinoma; Ovarian Adenocarcinoma; Lung AdenocarcinomaPromote immunityMesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable.
20635390Mesothelioma; Ovarian Carcinoma; Lung Adenocarcinoma; Pancreatic CarcinomaInhibit immunityMesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of mesothelioma, ovarian cancer and other malignant tumors. The interaction between mesothelin and CA125 (also called MUC16) may facilitate the implantation and metastasis of tumors in the peritoneal cavity.
Summary
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
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 MSLN 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
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
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 MSLN in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.2160.346
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2640.608
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.5670.171
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9161.7450.0882
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592.6560.127
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.580.757
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.7680.297
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.220.404
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3490.833
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.4350.707
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.4350.776
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0060.989
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MSLN 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) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103033.3-33.30.231
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
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) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382710.53.76.80.393
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221313.6013.60.279
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.27.1-0.91
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
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MSLN. 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
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MSLN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MSLN.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MSLN. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MSLN expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MSLN and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMSLN
Namemesothelin
Aliases MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MSLN collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting MSLN.
ID Name Drug Type Targets #Targets
DB12845AmatuximabBiotechMSLN1