Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
J Mol Med (Berl). 2021 Feb;99(2):193-212. doi: 10.1007/s00109-020-02015-5. Epub 2021 Jan 3.
Although gastric cancer (GC) is one of the most common cancers with high incidence and mortality rates, its pathogenesis is still not elucidated. GC carcinogenesis is complicated and involved in the activation of oncoproteins and inactivation of tumor suppressors. The ubiquitin-proteasome system (UPS) is crucial for protein degradation and regulation of physiological and pathological processes. E3 ubiquitin ligases are pivotal enzymes in UPS, containing various subfamily proteins. Previous studies report that some E3 ligases, including SKP2, CUL1, and MDM2, act as oncoproteins in GC carcinogenesis. On the other hand, FBXW7, FBXL5, FBXO31, RNF43, and RNF180 exert as tumor suppressors in GC carcinogenesis. Moreover, E3 ligases modulate cell growth, cell apoptosis, and cell cycle; thus, it is complicated to confer cisplatin resistance/sensitivity in GC cells. The intrinsic and acquired cisplatin resistance limits its clinical application against GC. In this review, we explore oncogenic and tumor suppressive roles of E3 ligases in GC carcinogenesis and focus on the effects of E3 ligases on cisplatin resistance in GC cells, which will provide novel therapeutic targets for GC therapy, especially for cisplatin-resistant patients.
虽然胃癌 (GC) 是一种发病率和死亡率都很高的最常见癌症之一，但它的发病机制仍不清楚。GC 的发生是复杂的，涉及癌蛋白的激活和肿瘤抑制因子的失活。泛素-蛋白酶体系统 (UPS) 对于蛋白质降解和生理及病理过程的调节至关重要。E3 泛素连接酶是 UPS 的关键酶，包含各种亚家族蛋白。先前的研究报告表明，一些 E3 连接酶，包括 SKP2、CUL1 和 MDM2，在 GC 发生过程中充当癌蛋白。另一方面，FBXW7、FBXL5、FBXO31、RNF43 和 RNF180 在 GC 发生过程中作为肿瘤抑制因子发挥作用。此外，E3 连接酶调节细胞生长、细胞凋亡和细胞周期；因此，GC 细胞中顺铂耐药/敏感性的赋予非常复杂。GC 对顺铂的固有和获得性耐药限制了其临床应用。在这篇综述中，我们探讨了 E3 连接酶在 GC 发生过程中的致癌和抑癌作用，并重点关注了 E3 连接酶对 GC 细胞顺铂耐药性的影响，这将为 GC 治疗，特别是顺铂耐药患者提供新的治疗靶点。
