Open AccessRIN 1 promotes renal cell carcinoma malignancy by activating EGFR signaling through Rab25
Author(s) -
Feng ZiHao,
Fang Yong,
Zhao LiangYun,
Lu Jun,
Wang YongQian,
Chen ZhenHua,
Huang Yong,
Wei JinHuan,
Liang YanPing,
Cen JunJie,
Pan YiHui,
Liao Bing,
Chen Wei,
Luo JunHang
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13297
Subject(s) - renal cell carcinoma , cancer research , malignancy , cell growth , gene knockdown , cell , metastasis , medicine , biology , pathology , cancer , cell culture , genetics
We previously identified the important role of RIN 1 expression in the prognosis of clear cell renal cell carcinoma (cc RCC ). The role of RIN 1 in cc RCC malignancy and underlying molecular mechanisms remain unclear. Here we report that cc RCC cells and tissues expressed more RIN 1 than normal controls. Gain‐of‐function and loss‐of‐function studies demonstrated that RIN 1 enhanced cc RCC cell growth, migration and invasion abilities in vitro and promoted tumor growth and metastasis in vivo . Mechanistic studies revealed that RIN 1 has an activating effect on EGFR signaling in cc RCC . In addition, we unveil Rab25, a critical GTP ase in cc RCC malignancy, as a functional RIN 1 interacting partner. Knockdown of Rab25 eliminated the augmentation of carcinoma cell proliferation, migration and invasion by ectopic RIN 1. We also confirmed that RIN 1 and Rab25 expression correlates with the overall‐survival of cc RCC patients from TCGA . These findings suggest that RIN 1 plays an important oncogenic role in cc RCC malignancy by activation of EGFR signaling through interacting with Rab25, and RIN 1 could be employed as an effective therapeutic target for cc RCC .