Overexpression of Rac GTPase Activating Protein 1 Contributes to Proliferation of Cancer Cells by Reducing Hippo Signaling to Promote Cytokinesis.

Gastroenterology
Xiao-Mei YangZhi-Gang Zhang

Abstract

Agents designed to block or alter cytokinesis can kill or stop proliferation of cancer cells. We aimed to identify cytokinesis-related proteins that are overexpressed in hepatocellular carcinoma (HCC) cells and might be targeted to slow liver tumor growth. Using the Oncomine database, we compared the gene expression patterns in 16 cancer microarray datasets and assessed gene enrichment sets using gene ontology. We performed immunohistochemical analysis of an HCC tissue microarray and identified changes in protein levels that are associated with patient survival times. Candidate genes were overexpressed or knocked down with small hairpin RNAs in SMMC7721, MHCC97H, or HCCLM3 cell lines; we analyzed their proliferation, viability, and clone-formation ability and their growth as subcutaneous or orthotopic xenograft tumors in mice. We performed microarray analyses to identify alterations in signaling pathways and immunoblot and immunofluorescence assays to detect and localize proteins in tissues. Yeast 2-hybrid screens and mass spectrometry combined with co-immunoprecipitation experiments were used to identify binding proteins. Protein interactions were validated with co-immunoprecipitation and proximity ligation assays. Chromatin i...Continue Reading

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Citations

Apr 14, 2019·Gut·Myriam Bou-NaderChantal Desdouets
Apr 25, 2020·Signal Transduction and Targeted Therapy·Lihui LiLijun Jia
Apr 3, 2019·International Journal of Molecular Sciences·Jinglin ZhangWei Kang
Aug 11, 2020·World Journal of Clinical Cases·Ru ZhengHua-Jie Cai
Jun 13, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Suet-Yan KwanWen Xue
Apr 27, 2021·Experimental Biology and Medicine·Yiting QiaoJianxiang Chen
Aug 3, 2021·Frontiers in Oncology·Lisa SuXiangdong Kong

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