The pro-survival Oct4/Stat1/Mcl-1 axis is associated with poor prognosis in lung adenocarcinoma patients

Yu Chu Su, Yi Cheng Chen, Yau Lin Tseng, Gia Shing Shieh, Pensee Wu, Ai Li Shiau, Chao Liang Wu

研究成果: Article同行評審

摘要

The embryonic stem cell marker Oct4 is expressed in several human cancers and is positively correlated with a poor outcome in cancer patients. However, its physiological role in cancer progression remains poorly understood. Tumor cells block apoptosis to escape cell death so that they can proliferate indefinitely, leading to ineffective therapy for cancer patients. In this study, we investigated whether Oct4 regulates the apoptosis pathway and contributes to poor prognosis in patients with lung adenocarcinoma. Our results revealed that Oct4 expression is correlated with Stat1 expression in lung adenocarcinoma patients and Oct4 is directly bound to the Stat1 promoter to transactivate Stat1 in lung adenocarcinoma cells. Expression of the Stat1 downstream gene Mcl-1 increased in Oct4-overexpressing cancer cells, while Stat1 knockdown in Oct4-overexpressing cancer cells sensitized them to cisplatin-induced apoptosis. Furthermore, Oct4 promoted Stat1 expression and tumor growth, whereas silencing of Stat1 reduced Oct4-induced tumor growth in human lung tumor xenograft models. Taken together, we demonstrate that Oct4 is a pro-survival factor by inducing Stat1 expression and that the Oct4/Stat1/Mcl-1 axis may be a potential therapeutic target for lung adenocarcinoma.

原文English
文章編號2642
期刊Cells
10
發行號10
DOIs
出版狀態Published - 2021 十月

All Science Journal Classification (ASJC) codes

  • 醫藥 (全部)

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