Physical interaction of STAT1 isoforms with TGF-β receptors leads to functional crosstalk between two signaling pathways in epithelial ovarian cancer

Journal of Experimental & Clinical Cancer Research : CR
Xiaoling TianGuoxiong Xu

Abstract

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. 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. 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 ...Continue Reading

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Citations

Mar 28, 2019·Journal of Ovarian Research·Hadis ZareZatollah Asemi
Dec 12, 2018·Journal of Cellular Physiology·Amirhossein AhmadiKeywan Mortezaee
May 20, 2020·Therapeutic Advances in Medical Oncology·Jinguo ZhangGuoxiong Xu
Oct 13, 2020·Cancer Biology & Therapy·Fangran LiuGuoxiong Xu
Nov 27, 2020·International Journal of Molecular Sciences·Eleonora A BragaNikolay E Kushlinskii
Apr 10, 2021·Frontiers in Cell and Developmental Biology·Xin LiGuoxiong Xu
Aug 2, 2021·Journal of Thrombosis and Haemostasis : JTH·Amir AsgariPaul Jurasz

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Methods Mentioned

BETA
PCR
transfection
co-immunoprecipitation
Protein Assay
immunoprecipitation

Software Mentioned

SPSS Statistics
GraphPad Prism
GIS ID Analysis

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