Wenxia Wei, Baifu Qin, Weijie Wen, Boyu Zhang, Haidan Luo, Yuzhi Wang, Hui Xu, Xiaoshan Xie, Sicheng Liu, Xin Jiang, Mengan Wang, Qin Tang, Jiayu Zhang, Runxiang Yang, Zongmin Fan, Haiwen Lyu, Junzhong Lin, Kai Li, Mong-Hong Lee
Continuous de novo fatty acid synthesis is required for the biosynthetic demands of tumor. FBXW7 is a highly mutated gene in CRC, but its biological functions in cancer are not fully characterized. Here, we report that FBXW7β, a FBXW7 isoform located in the cytoplasm and frequently mutated in CRC, is an E3 ligase of fatty acid synthase (FASN). Cancer-specific FBXW7β mutations that could not degrade FASN can lead to sustained lipogenesis in CRC. COP9 signalosome subunit 6 (CSN6), an oncogenic marker of CRC, increases lipogenesis via interacting with and stabilizing FASN...
May 19, 2023: Signal Transduction and Targeted Therapy