USP11 induce resistance to 5-Fluorouracil in Colorectal Cancer through activating autophagy by stabilizing VCP

USP11 通过稳定 VCP 激活自噬,诱导结直肠癌对 5-氟尿嘧啶产生耐药性

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作者:Hongze Sun, Rangrang Wang, Yuan Liu, Haitao Mei, Xueni Liu, Zhihai Peng

Abstract

Chemotherapy plays an important role in the treatment of patients with colorectal cancer (CRC). However, the resistance to chemotherapy severely affects the prognosis of CRC patients and the mechanisms are still poorly understood. Our study investigated the role of ubiquitin-specific protease 11 (USP11) in CRC chemotherapy and found that USP11 could induce resistance to 5-fluorouracil by activating autophagy. A series of in vitro and in vivo experiments revealed that USP11 promoted autophagy through AMPK/Akt/mTOR pathway via stabilizing valosin-containing protein (VCP). Overall, our study demonstrated that USP11 might be valuable to predict the chemotherapeutic sensitivity and improve the prognosis of CRC patients.

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