Liu Hao, Jia Xiaoting, Luo Kai, Chen Xiangzhou, Zhang Zhijie, Chen Danyang, Gu Yixue, He Zhimin, Zheng Guopei
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
Oncogenesis. 2022 Apr 22;11(1):19. doi: 10.1038/s41389-022-00392-9.
Previously, our lab explored that tongue cancer resistance-associated protein (TCRP1) plays a central role in cancer chemo-resistance and progression. Absolutely, TCRP1 was significantly increased in lung cancer. But the mechanism is far from elucidated. Here, we found that TCRP1 was increased in p53-mutant non-small-cell lung cancer (NSCLC), comparing to that in NSCLC with wild type p53. Further study showed that mutant p53 couldn't bind to the promoter of TCRP1 to inhibit its expression. While the wild type p53 did so. Next, loss-and gain-of-function assays demonstrated that TCRP1 promoted cell proliferation and tumor growth in NSCLC. Regarding the mechanism, TCRP1 encouraged AKT phosphorylation and blocked FOXO3a nuclear localization through favoring FOXO3a ubiquitination in cytoplasm, thus, promoted cell cycle progression. Conclusionly, TCRP1 was upregulated in NSCLC cells with mutant p53. TCRP1 promoted NSCLC progression via regulating cell cycle.
此前，我们实验室研究发现舌癌耐药相关蛋白（TCRP1）在癌症化疗耐药和进展中起核心作用。确实，TCRP1在肺癌中显著升高。但其机制仍远未阐明。在此，我们发现与野生型p53的非小细胞肺癌（NSCLC）相比，TCRP1在p53突变的非小细胞肺癌中升高。进一步研究表明，突变型p53不能结合TCRP1的启动子来抑制其表达。而野生型p53则可以。接下来，功能缺失和功能获得实验表明，TCRP1促进NSCLC细胞增殖和肿瘤生长。关于其机制，TCRP1通过促进FOXO3a在细胞质中的泛素化来促进AKT磷酸化并阻止FOXO3a核定位，从而促进细胞周期进程。总之，TCRP1在p53突变的NSCLC细胞中上调。TCRP1通过调节细胞周期促进NSCLC进展。
