{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tian X"],"funding":["Science and Technology Commission of Shanghai Municipality","Natural Science Foundation of Shanghai","National Natural Science Foundation of China","Shanghai Municipal Commission of Health and Family Planning","Committee of Science and Technology of Jinshan District"],"pagination":["103"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5948853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["37(1)"],"pubmed_abstract":["<h4>Background</h4>The signal transducer and activator of transcription (STAT) and transforming growth factor-β (TGF-β) signaling pathways play important roles in epithelial ovarian cancer (EOC). However, the mechanism of crosstalk between two pathways is not completely understood.<h4>Methods</h4>The expression of STAT1 protein was detected by tissue microarray and immunoblotting (IB). The interaction of STAT1 isoforms with TGF-β receptors was confirmed by immunoprecipitation and IB. The effect of TGF-β signaling on STAT1 activation was examined in EOC and non-tumorous HOSEpiC cells treated with TGF-β1 in the presence or absence of the inhibitor of TGF-β type I receptor. The gain-of-function and loss-of-function approaches were applied for detecting the role of STAT1 on EOC cell behaviours.<h4>Results</h4>The high level of STAT1 was observed in patients with high-grade serous EOC. STAT1 expression was higher in ovarian cancer cells than noncancerous cells. TGF-β1 activated the STAT1 pathway by inducing the phosphorylation of STAT1α on S727 residue. The full-length STAT1α and the truncated STAT1β directly interacted with TGF-β receptors (ALK1/ALK5 and TβRII), which was mediated by TGF-β1. STAT1α and STAT1β blocked the activation of the TGF-β1 signaling pathway in EOC cells by reducing Smad2 phosphorylation. STAT1 overexpression induced EOC cell proliferation, migration, and invasion; whereas its inhibition enhanced TGF-β1-induced phospho-Smad2 and suppressed EOC cell proliferation, migration, and invasion.<h4>Conclusions</h4>Our data unveil a novel insight into the molecular mechanism of crosstalk between the STAT1 and TGF-β signaling pathways, which affected the cancer cell behavior. Suppression of STAT1 may be a potential therapeutic strategy for targeting ovarian cancer."],"journal":["Journal of experimental & clinical cancer research : CR"],"pubmed_title":["Physical interaction of STAT1 isoforms with TGF-β receptors leads to functional crosstalk between two signaling pathways in epithelial ovarian cancer."],"pmcid":["PMC5948853"],"funding_grant_id":["201640287","81272880","17ZR1404100","JSKJ-KTMS-2015-01","124119b1300"],"pubmed_authors":["Ren W","Lin Q","Nadeem L","Guan W","Tian X","Zhou D","Zhang L","Sun W","Xu G"],"additional_accession":[]},"is_claimable":false,"name":"Physical interaction of STAT1 isoforms with TGF-β receptors leads to functional crosstalk between two signaling pathways in epithelial ovarian cancer.","description":"<h4>Background</h4>The signal transducer and activator of transcription (STAT) and transforming growth factor-β (TGF-β) signaling pathways play important roles in epithelial ovarian cancer (EOC). However, the mechanism of crosstalk between two pathways is not completely understood.<h4>Methods</h4>The expression of STAT1 protein was detected by tissue microarray and immunoblotting (IB). The interaction of STAT1 isoforms with TGF-β receptors was confirmed by immunoprecipitation and IB. The effect of TGF-β signaling on STAT1 activation was examined in EOC and non-tumorous HOSEpiC cells treated with TGF-β1 in the presence or absence of the inhibitor of TGF-β type I receptor. The gain-of-function and loss-of-function approaches were applied for detecting the role of STAT1 on EOC cell behaviours.<h4>Results</h4>The high level of STAT1 was observed in patients with high-grade serous EOC. STAT1 expression was higher in ovarian cancer cells than noncancerous cells. TGF-β1 activated the STAT1 pathway by inducing the phosphorylation of STAT1α on S727 residue. The full-length STAT1α and the truncated STAT1β directly interacted with TGF-β receptors (ALK1/ALK5 and TβRII), which was mediated by TGF-β1. STAT1α and STAT1β blocked the activation of the TGF-β1 signaling pathway in EOC cells by reducing Smad2 phosphorylation. STAT1 overexpression induced EOC cell proliferation, migration, and invasion; whereas its inhibition enhanced TGF-β1-induced phospho-Smad2 and suppressed EOC cell proliferation, migration, and invasion.<h4>Conclusions</h4>Our data unveil a novel insight into the molecular mechanism of crosstalk between the STAT1 and TGF-β signaling pathways, which affected the cancer cell behavior. Suppression of STAT1 may be a potential therapeutic strategy for targeting ovarian cancer.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 May","modification":"2026-05-05T22:37:53.471Z","creation":"2019-03-26T23:37:50Z"},"accession":"S-EPMC5948853","cross_references":{"pubmed":["29751820"],"doi":["10.1186/s13046-018-0773-8"]}}