FoxO3 inactivation promotes human cholangiocarcinoma tumorigenesis and chemoresistance through Keap1‐Nrf2 signaling
Li Guan, Lei Zhang, Zhicheng Gong, Xiaonan Hou, Yuxiu Xu, Xinhua Feng, Hongyang Wang, Han You – 9 February 2016 – FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch‐like ECH‐associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation.