RIN 1 promotes renal cell carcinoma malignancy by activating EGFR signaling through Rab25

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 cont...

Full description

Saved in:
Bibliographic Details
Published in:Cancer science 2017-08, Vol.108 (8), p.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: Article
Language:English
Subjects:
Cell adhesion & migration
Cell migration
Cell proliferation
Clear cell-type renal cell carcinoma
Epidermal growth factor receptors
Guanosine triphosphatases
Kidney cancer
Kinases
Malignancy
Medical prognosis
Metastases
Metastasis
Molecular modelling
Patients
Proteins
R&D
Research & development
Therapeutic applications
Tumorigenesis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 .
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.13297