Song Li, Zhang Lin, Zhou Yun, Shao Xiaotong, Xu Yuting, Pei Dongsheng, Wang Qingling
Department of Pathology, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
Department of Radiation Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221000, China.
Cell Death Discov. 2022 Apr 21;8(1):219. doi: 10.1038/s41420-022-01023-3.
ORP5, a lipid transporter, has been reported to increase the metastasis of several cancers. However, the potential mechanisms of ORP5 in renal cell carcinoma (RCC) remain unclear. In this study, we demonstrated that ORP5 was commonly overexpressed in tumor cells and tissues of RCC, and associated with tumor progression. Overexpression of ORP5 could promote RCC cells migration and invasion. In addition, the results suggested that the expression of ORP5 was favorably associated with c-Met expression, and ORP5 promoted RCC cells metastasis by upregulating c-Met in vitro and in vivo. Mechanistically, ORP5 facilitated the ubiquitination and degradation of c-Cbl (the E3 ligase of c-Met), and thus inhibited c-Met lysosomal degradation, which resulted in the stabilization of c-Met. In general, these findings revealed the role of ORP5 in contributing to tumorigenesis via upregulating c-Met in RCC.
氧化还原电位蛋白5（ORP5）是一种脂质转运蛋白，据报道它会增加几种癌症的转移。然而，ORP5在肾细胞癌（RCC）中的潜在机制仍不清楚。在本研究中，我们证明ORP5在RCC的肿瘤细胞和组织中普遍过表达，并与肿瘤进展相关。ORP5的过表达可促进RCC细胞的迁移和侵袭。此外，结果表明ORP5的表达与c-Met表达呈正相关，并且ORP5在体外和体内通过上调c-Met促进RCC细胞转移。从机制上讲，ORP5促进了c-Cbl（c-Met的E3连接酶）的泛素化和降解，从而抑制了c-Met的溶酶体降解，导致c-Met的稳定。总体而言，这些发现揭示了ORP5通过上调RCC中的c-Met在肿瘤发生中的作用。
