c-Fos regulated by TMPO/ERK axis promotes 5-FU resistance via inducing NANOG transcription in colon cancer.

Yanping Gui, Xiaoping Qian, Youxiang Ding, Qianqian Chen, Fangyu Ye, Yuting Ye, Yingjian Hou, Jun Yu, Li Zhao

Cell death & disease 2024 Jan 17

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Acquired drug resistance is one of the most common limitations for the clinical response of colon cancer to 5-Fluorouracil (5-FU)-based chemotherapy. The relevant molecular mechanisms might be diversity, but still not be elucidated clearly. In this study, we aimed to investigate the potential mechanisms of c-Fos, a subfamily of activator protein-1, in 5-FU chemoresistance. We determined that phosphorylated c-Fos promoted colon cancer cells resistance to 5-FU by facilitating the cancer stemness. Mechanically, 5-FU treatment induced autolysosome-dependent degradation of TMPO, which subsequently triggered ERK-mediated phosphorylation of c-Fos. Additionally, c-Fos was found to bind to the promoter of NANOG and phosphorylation of c-Fos at Ser 374 was required for its regulation of NANOG expression. NANOG ablation impaired c-Fos/p-c-Fos induced 5-FU resistance and stemness. Taken together, these findings revealed that TMPO-mediated phosphorylation of c-Fos conferred 5-FU resistance by regulating NANOG expression and promoting cell stemness in colon cancer cells. c-Fos could be as a therapeutic target for colon cancer. © 2024. The Author(s).

Citation

Yanping Gui, Xiaoping Qian, Youxiang Ding, Qianqian Chen, Fangyu Ye, Yuting Ye, Yingjian Hou, Jun Yu, Li Zhao. c-Fos regulated by TMPO/ERK axis promotes 5-FU resistance via inducing NANOG transcription in colon cancer. Cell death & disease. 2024 Jan 17;15(1):61