J Cancer 2021; 12(8):2317-2325. doi:10.7150/jca.52158

Research Paper

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

Hongze Sun1,2#, Rangrang Wang1#, Yuan Liu1#, Haitao Mei1, Xueni Liu1✉, Zhihai Peng1,3✉

1. Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.
3. Department of General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
#These authors contributed equally to this work.

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Citation:
Sun H, Wang R, Liu Y, Mei H, Liu X, Peng Z. USP11 induce resistance to 5-Fluorouracil in Colorectal Cancer through activating autophagy by stabilizing VCP. J Cancer 2021; 12(8):2317-2325. doi:10.7150/jca.52158. Available from https://www.jcancer.org/v12p2317.htm

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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.

Keywords: USP11, VCP, colorectal cancer, 5-fluorouracil, chemotherapy resistance