Mengmeng Wang, Zhoudong Zhang, Mengxi Chen, Yixin Lv, Sheng Tian, Fanyi Meng, Yawen Zhang, Xuqin Guo, Yinshuang Chen, Man Yang, Jiawei Li, Tian Qiu, Fang Xu, Zhi Li, Qi Zhang, Jie Yang, Jing Sun, Hongjian Zhang, Haiyang Zhang, Huanqiu Li, Weipeng Wang
Metastatic colorectal cancer (mCRC) is a major cause of cancer-related mortality due to the absence of effective therapeutics. Thus, it is urgent to discover new drugs for mCRC. Fucosyltransferase 8 (FUT8) is a potential therapeutic target with high level in most malignant cancers including CRC. FUT8 mediates the core fucosylation of CD276 (B7-H3), a key immune checkpoint molecule (ICM), in CRC. FUT8-silence-induced defucosylation at N104 on B7-H3 attracts heat shock protein family A member 8 (HSPA8, also known as HSC70) to bind with 106-110 SLRLQ motif and consequently propels lysosomal proteolysis of B7-H3 through the chaperone-mediated autophagy (CMA) pathway...
August 3, 2023: Cell Death & Disease