Sun Aiqin, Chen Yifei, Tian Xianyan, Lin Qiong
School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Biomedicines. 2023 Feb 7;11(2):478. doi: 10.3390/biomedicines11020478.
Colorectal cancer (CRC) is estimated to rank as the second reason for cancer-related deaths, and the prognosis of CRC patients remains unsatisfactory. Numerous studies on gastrointestinal cell biology have shown that the E3 ligase-mediated ubiquitination exerts key functions in the pathogenesis of CRC. The homologous to E6-associated protein C-terminus (HECT) family E3 ligases are a major group of E3 enzymes, featured with the presence of a catalytic HECT domain, which participate in multiple cellular processes; thus, alterations in HECT E3 ligases in function or expression are closely related to the occurrence and development of many human malignancies, including-but not limited to-CRC. In this review, we summarize the potential role of HECT E3 ligases in colorectal carcinogenesis and the related underlying molecular mechanism to expand our understanding of their pathological functions. Exploiting specific inhibitors targeting HECT E3 ligases could be a potential therapeutic strategy for CRC therapy in the future.
据估计，结直肠癌（CRC）是癌症相关死亡的第二大原因，CRC患者的预后仍不尽人意。众多关于胃肠道细胞生物学的研究表明，E3连接酶介导的泛素化在CRC的发病机制中发挥关键作用。与E6相关蛋白C末端同源（HECT）家族E3连接酶是E3酶的主要类别，其特征是存在催化性HECT结构域，参与多种细胞过程；因此，HECT E3连接酶在功能或表达上的改变与许多人类恶性肿瘤的发生和发展密切相关，包括但不限于CRC。在本综述中，我们总结了HECT E3连接酶在结直肠癌发生中的潜在作用以及相关的潜在分子机制，以扩展我们对其病理功能的理解。开发针对HECT E3连接酶的特异性抑制剂可能是未来CRC治疗的一种潜在策略。
