Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, China.
Department of Ultrasound, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, China.
Life Sci. 2021 Jan 1;264:118711. doi: 10.1016/j.lfs.2020.118711. Epub 2020 Nov 10.
We investigated the association between c-Src and the progression of hepatocellular carcinoma (HCC) and its underlying mechanisms. The relationship between c-Src expression and the occurrence and development of HCC was explored using GEPIA and further confirmed by western blotting analysis and real-time quantitative PCR. CCK-8, flow cytometry, Transwell, and wound-healing assays were conducted to analyze the effects of c-Src on the growth, cell cycle, apoptosis, migration, and infiltration of HCC cells. Mouse models of transplanted xenogeneic human tumors were constructed to explore the effects of c-Src on HCC tumor growth. Compared with that in adjacent normal liver tissues, the expression level of c-Src in HCC tissues was significantly increased and was negatively correlated with patient survival. These findings are consistent with those in the GEPIA database. Downregulation of c-Src expression can inhibit the growth, infiltration, and migration of HCC cells. c-Src impeded the translocation of YAP from the nucleus to the cytoplasm and promoted Yes-associated protein transcriptional activity. In vivo experiments showed that c-Src inhibition suppressed tumor growth in mice. We found that c-Src can promote the growth and tumorigenesis of HCC cells by activating the Hippo signaling pathway.
我们研究了 c-Src 与肝细胞癌 (HCC) 进展的关系及其潜在机制。使用 GEPIA 探讨了 c-Src 表达与 HCC 发生和发展的关系，并通过 Western blot 分析和实时定量 PCR 进一步证实。通过 CCK-8、流式细胞术、Transwell 和划痕愈合实验分析了 c-Src 对 HCC 细胞生长、细胞周期、凋亡、迁移和浸润的影响。构建了移植异种人肿瘤的小鼠模型，以探讨 c-Src 对 HCC 肿瘤生长的影响。与相邻正常肝组织相比，HCC 组织中 c-Src 的表达水平显著升高，与患者的生存呈负相关。这些发现与 GEPIA 数据库中的结果一致。下调 c-Src 的表达可以抑制 HCC 细胞的生长、浸润和迁移。c-Src 阻止 YAP 从细胞核向细胞质易位，并促进 Yes 相关蛋白转录活性。体内实验表明，c-Src 抑制可抑制小鼠肿瘤生长。我们发现 c-Src 通过激活 Hippo 信号通路促进 HCC 细胞的生长和肿瘤发生。
