RIN1 promotes renal cell carcinoma malignancy by activating EGFR signaling through Rab25

• Published in: Cancer science Vol. 108; no. 8; pp. 1620 - 1627
• Main Authors: Feng, Zi‐Hao, Fang, Yong, Zhao, Liang‐Yun, Lu, Jun, Wang, Yong‐Qian, Chen, Zhen‐Hua, Huang, Yong, Wei, Jin‐Huan, Liang, Yan‐Ping, Cen, Jun‐Jie, Pan, Yi‐Hui, Liao, Bing, Chen, Wei, Luo, Jun‐Hang
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.08.2017
• Subjects: Animals; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; EGFR signaling; ErbB Receptors - metabolism; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Mice; Neoplasm Metastasis; Neoplasm Transplantation; Original; rab GTP-Binding Proteins - metabolism; Rab25; renal cell carcinoma; RIN1; Signal Transduction; Survival Analysis; tumorigenesis; Up-Regulation; EGFR signaling; renal cell carcinoma; tumorigenesis; RIN1; Rab25
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13297

We previously identified the important role of RIN1 expression in the prognosis of clear cell renal cell carcinoma (ccRCC). The role of RIN1 in ccRCC malignancy and underlying molecular mechanisms remain unclear. Here we report that ccRCC cells and tissues expressed more RIN1 than normal controls. Gain‐of‐function and loss‐of‐function studies demonstrated that RIN1 enhanced ccRCC cell growth, migration and invasion abilities in vitro and promoted tumor growth and metastasis in vivo. Mechanistic studies revealed that RIN1 has an activating effect on EGFR signaling in ccRCC. In addition, we unveil Rab25, a critical GTPase in ccRCC malignancy, as a functional RIN1 interacting partner. Knockdown of Rab25 eliminated the augmentation of carcinoma cell proliferation, migration and invasion by ectopic RIN1. We also confirmed that RIN1 and Rab25 expression correlates with the overall‐survival of ccRCC patients from TCGA. These findings suggest that RIN1 plays an important oncogenic role in ccRCC malignancy by activation of EGFR signaling through interacting with Rab25, and RIN1 could be employed as an effective therapeutic target for ccRCC. In the current study, we found that silencing Rab25 inhibited EGFR signalling and strikingly reversed the ability of RIN1‐overexpressing ccRCC cells to proliferation, migration and invasion in vitro. Gain‐ and loss‐of‐function studies demonstrated that RIN1 enhanced ccRCC cell growth, migration and invasion abilities in vitro and promoted tumor growth and metastasis in vivo.