CBLC(CBL原癌基因C)是E3泛素蛋白连接酶,在癌症中起关键作用。然而,CBLC在结直肠癌(CRC)中的作用和机制尚未完全阐明。本研究的目的是探讨CBLC在CRC中的功能及其潜在的分子机制。高CBLC水平在CRC患者的肿瘤组织中得到证实,其表达与TNM分期呈正相关。接下来,我们使用功能的获得或丧失探讨了CBLC在CRC中的作用.对于生物功能分析,CCK-8细胞增殖,菌落形成,流式细胞术,划痕,和transwell分析共同表明CBLC过表达促进细胞增殖,细胞周期进程,移民和入侵。正如观察到的,CBLC敲除表现出完全相反的效果,导致体外致瘤性受损。异种移植研究表明,CBLC过表达加速肿瘤生长并促进肿瘤向肺转移,同时证实了CBLC敲低对CRC细胞的致瘤性和转移能力的抑制作用。此外,探讨了CBLC在CRC中的分子机制。CBLC诱导激活ERK信号通路,进一步导致其促肿瘤作用。值得注意的是,CBLC通过其泛素连接酶活性降低ABI1(Abelson相互作用蛋白1,候选肿瘤抑制因子)蛋白水平,而ABI1上调消除了CBLC对CRC肿瘤发生的影响。一起来看,这些结果表明,CBLC通过触发ABI1的泛素化和降解以及激活ERK信号通路,在CRC中充当肿瘤启动子.CBLC可能是CRC的潜在新靶标。
CBLC (CBL proto-oncogene C) is an E3 ubiquitin protein ligase that plays a key role in cancers. However, the function and mechanism of CBLC in colorectal cancer (CRC) has not been fully elucidated. The aim of this study was to investigate the function of CBLC in CRC and its underlying molecular mechanism. High CBLC levels were certified in tumor tissues of CRC patients, and its expression was positively associated with TNM stage. Next, we explored the role of CBLC in CRC using gain or loss of function. For biological function analysis, CCK-8 cell proliferation, colony formation, flow cytometry, scratch, and transwell assays collectively suggested that CBLC overexpression promoted cell proliferation, cell cycle progression, migration and invasion. As observed, CBLC knockdown exhibited exactly opposite effects, resulting in impaired tumorigenicity in vitro. Xenograft studies displayed that CBLC overexpression accelerated tumor growth and promoted tumor metastasis to the lung, while the inhibitory effects of CBLC knockdown on tumorigenicity and metastasis ability of CRC cells was also confirmed. Furthermore, the molecular mechanism of CBLC in CRC was explored. CBLC induced the activation of ERK signaling pathway, further leading to its pro-tumor role. Notably, CBLC decreased
ABI1 (Abelson interactor protein-1, a candidate tumor suppressor) protein levels through its ubiquitin ligase activity, while
ABI1 upregulation abolished the effects of CBLC on the tumorigenesis of CRC. Taken together, these results demonstrate that CBLC acts as a tumor promoter in CRC through triggering the ubiquitination and degradation of
ABI1 and activating the ERK signaling pathway. CBLC may be a potential novel target for CRC.