Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China.
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Dig Dis Sci. 2023 Aug;68(8):3312-3323. doi: 10.1007/s10620-023-07995-1. Epub 2023 Jun 13.
Emerging evidence showed that FAT10 is a vital regulator of tumor occurrence and development. The molecular mechanisms underlying the specific role of FAT10 in colorectal cancer (CRC) are not yet known.
To investigate whether FAT10 participates in the proliferation, invasion and metastasis of CRC.
This study investigated the function and clinical significance of FAT10 protein expression in CRC. Furthermore, over-expression and knockdown experiments of FAT10 were developed to explore their effects on CRC cell migration and proliferation. Moreover, a molecular mechanism of FAT10 regulate calpain small subunit 1(Capn4) was explored.
In this research, the FAT10 expression level was elevated in CRC tissues compared to corresponding normal tissues. In addition, the elevated FAT10 expression level is significantly linked to advanced clinical stage and poor CRC prognosis. Furthermore, a very high expression of FAT10 was observed in CRC cells, and FAT10 overexpression significantly enhanced the in vivo proliferation, invasion, and metastasis of the cells, whereas knockdown of FAT10 inhibited all these cellular factors in both in vivo and in vitro environments. Moreover, the outcomes of this study suggested that FAT10 enhances colorectal cancer progression through enhancement of Capn4 expression, leading to the progression of various human tumors, as reported by previous research. The mechanism via which FAT10 promotes CRC cells proliferation, invasion, and metastasis involves modification of the ubiquitination and degradation processes of Capn4.
FAT10 is a vital regulator of the tumorigenesis and advancement of CRC, thus serving as a promising pharmaceutical target for treating CRC patients.
新出现的证据表明，FAT10 是肿瘤发生和发展的重要调节因子。FAT10 在结直肠癌（CRC）中发挥特定作用的分子机制尚不清楚。
研究 FAT10 是否参与 CRC 的增殖、侵袭和转移。
本研究调查了 FAT10 蛋白表达在 CRC 中的功能和临床意义。此外，还进行了 FAT10 的过表达和敲低实验，以探讨其对 CRC 细胞迁移和增殖的影响。此外，还探讨了 FAT10 调节钙蛋白酶小亚基 1（Capn4）的分子机制。
在这项研究中，与相应的正常组织相比，CRC 组织中的 FAT10 表达水平升高。此外，FAT10 表达水平的升高与 CRC 的晚期临床分期和不良预后显著相关。此外，在 CRC 细胞中观察到 FAT10 的高表达，FAT10 的过表达显著增强了细胞在体内的增殖、侵袭和转移，而 FAT10 的敲低则抑制了体内和体外环境中所有这些细胞因子。此外，本研究的结果表明，FAT10 通过增强 Capn4 的表达来增强结直肠癌细胞的进展，从而促进各种人类肿瘤的进展，正如先前的研究报道。FAT10 促进 CRC 细胞增殖、侵袭和转移的机制涉及对 Capn4 的泛素化和降解过程的修饰。
FAT10 是 CRC 发生和发展的重要调节因子，因此是治疗 CRC 患者的有前途的药物靶点。
