%0 Journal Article
%T STAT1¦Â enhances STAT1 function by protecting STAT1¦Á from degradation in esophageal squamous cell carcinoma
%A Hailong Yun
%A Min Su
%A Raymond Lai
%A Yelong Chen
%A Ying Zhang
%A Zhaoyong Liu
%J Archive of "Cell Death & Disease".
%D 2017
%R 10.1038/cddis.2017.481
%X STAT1, which carries tumor suppressor functions in several models, consists of two isoforms, namely STAT1¦Á and STAT1¦Â. The biological function and significance of STAT1¦Â has never been examined in human cancer. We examined STAT1¦Â function in esophageal squamous cell carcinoma (ESCC) by transfecting a STAT1¦Â gene into various ESCC cell lines. The interaction between STAT1¦Á and STAT1¦Â was examined by using co-immunoprecipitation and confocal microscopy. The prognostic significance of STAT1¦Â expression, detectable by immunohistochemistry and western blot, was evaluated in a large cohort of ESCC patients. Enforced expression of STAT1¦Â induced and prolonged the expression and phosphorylation of STAT1¦Á in ESCC cells, and these effects were amplified by gamma-interferon (IFN-¦Ã). We also found that STAT1¦Â interacts with STAT1¦Á and decreases STAT1¦Á degradation by the proteasome. Moreover, STAT1¦Â substantially increased the DNA binding and transcription activity of STAT1. STAT1¦Â also sensitized ESCC cells to chemotherapeutic agents, including cisplatin and 5-flurouracil. Using western blot and immunohistochemistry, we found that STAT1¦Â was frequently decreased in esophageal cancer, as compared to their adjacent benign esophageal epithelial tissue. Loss of STAT1¦Â significantly correlated with lymph node metastasis, invasion and shorter overall survival in ESCC patients. Therefore, STAT1¦Â plays a key role in enhancing the tumor suppressor function of STAT1¦Á, in ESCC, in a manner that can be amplified by IFN-¦Ã
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682650/