AUTHOR=Gao Shenglin , Gao Lei , Wang Simin , Shi Xiaokai , Yue Chuang , Wei Shuzhang , Zuo Li , Zhang Lifeng , Qin Xihu 

TITLE=ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.618987

DOI=10.3389/fcell.2021.618987

ISSN=2296-634X

ABSTRACT=Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant cancers in East Asia, with high incidence and mortality. Accumulating evidence shows that ATF3 is associated with tumor progression. 
Methods: The expression of ATF3 in ccRCC was detected in 93 ccRCC patients by qPCR, including 24 paired normal and tumor tissues used to further compare the expression by WB, and IHC. ccRCC and normal kidney cell lines were used. Lentivirus was used to overexpression or knockdown ATF3, and the following function alteration was detected by CCK8, colony formation, wound healing, invasion assay and flow cytometer. The potential mechanism impacted by ATF3 was analyzed by GSEA, and verified by WB, invasion or immunofluorescence assay. What’s more, xenograft mouse model was performed to assess the function of ATF3 in vivo.
Results: ATF3 was significantly decreased compared to adjacent normal tissues in ccRCC. Through gain and loss of function methods in vitro assay, we found that ATF3 could regulate proliferation, cycle progression, migration and invasion of ccRCC cells. As to the in vivo part, the xenograft mouse model disclosed that the overexpression of ATF3 could inhibit tumor growth of ccRCC. Moreover, the mechanism analysis showed that suppressed ATF3 could increase the expression of β-catenin and promoted β-catenin transfer to the nucleus, if which might impact by EGFR/AKT/GSK3β signaling. 
Conclusion: ATF3 could be utilized as an independent protective factor to inhibit the progression of ccRCC. Potential treatment strategy for ccRCC by the concern of ATF3/EGFR/AKT/ GSK3β /β‐catenin signaling pathway.