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ETV4 is a theranostic target in clear cell renal cell carcinoma that promotes metastasis by activating the pro-metastatic gene FOSL1 in a PI3K-AKT dependent manner.

Cancer letters (2020-04-20)
Liang Xu, Hao Hu, Li-Sheng Zheng, Meng-Yao Wang, Yan Mei, Li-Xia Peng, Yuan-Yuan Qiang, Chang-Zhi Li, Dong-Fang Meng, Ming-Dian Wang, Zhi-Jie Liu, Xin-Jian Li, Bi-Jun Huang, Chao-Nan Qian
ABSTRACT

Distant metastasis is the major cause of short survival in ccRCC patients. However, the development of effective therapies for metastatic ccRCC is limited. Herein, we reported that ETV4 was selected from among 150 relevant genes with in vivo evidence of promoting metastasis. In this study, we identified that ETV4 promoted ccRCC cell migration and metastasis in vitro and in vivo, and a positive correlation between ETV4 and FOSL1 expression was found in ccRCC tissues and cell lines. Further investigation suggested that ETV4 increase FOSL1 expression through direct binding with the FOSL1 promoter. Furthermore, ETV4/FOSL1 was proved as a novel upstream and downstream causal relationship in ccRCC in an AKT dependent manner. In addition, both ETV4 and FOSL1 serve as an independent, unfavorable ccRCC prognostic indicator, and the accumulation of the ETV4 and FOSL1 in ccRCC patients result in a worse survival outcome in ccRCC patients. Taken together, our results suggest that the ETV4/FOSL1 axis acts as a prognostic biomarker and ETV4 directly up-regulates FOSL1 by binding with its promoter in a PI3K-AKT dependent manner, leading to metastasis and disease progression of ccRCC.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
TRI Reagent®, For processing tissues, cells cultured in monolayer or cell pellets
Sigma-Aldrich
TE Buffer - for use in ChIP Assays, For use in Chromatin Immunoprecipitation assays.
Sigma-Aldrich
SDS Lysis Buffer - for use in ChIP Assay, For use in Chromatin Immunoprecipitation assays.