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The Pro-Survival Oct4/Stat1/Mcl-1 Axis Is Associated with Poor Prognosis in Lung Adenocarcinoma Patients

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

The Pro-Survival Oct4/Stat1/Mcl-1 Axis Is Associated with Poor Prognosis in Lung Adenocarcinoma Patients Thumbnail


Authors

Yu-Chu Su

Yi-Cheng Chen

Yau-Lin Tseng

Gia-Shing Shieh

Ai-Li Shiau

Chao-Liang Wu



Abstract

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.

Journal Article Type Article
Acceptance Date Sep 28, 2021
Online Publication Date Oct 3, 2021
Publication Date Oct 3, 2021
Publicly Available Date May 30, 2023
Journal Cells
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 10
Issue 10
Article Number 2642
DOI https://doi.org/10.3390/cells10102642
Keywords lung adenocarcinoma; anti-apoptosis; cell survival; Oct4; Stat1; Mcl-1
Publisher URL https://doi.org/10.3390/cells10102642

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