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About the Authors:
Shruthy Suresh
Affiliation: Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, United States of America
Deniz Durakoglugil
Affiliation: Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, United States of America
ORCID http://orcid.org/0000-0003-2393-7528
Xiaorong Zhou
Affiliations Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, United States of America, Department of Immunology, Nantong University School of Medicine, Nantong, China
Bokai Zhu
Affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America
ORCID http://orcid.org/0000-0003-0827-5757
Sarah A. Comerford
Affiliation: Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX, United States of America
Chao Xing
Affiliations Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, United States of America, McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX, United States of America
Xian-Jin Xie
Affiliations Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, United States of America, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, United States of America
ORCID http://orcid.org/0000-0002-5698-0330
Brian York
Affiliations Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States of America
Kathryn A. O’Donnell
* E-mail: [email protected]
Affiliations Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, United States of America, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, United States of AmericaAbstract
Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis. To determine if genetic loss of SRC-2 is sufficient to accelerate MYC-mediated liver tumorigenesis, we bred Src-2-/- mice with a MYC-induced liver tumor model and observed a significant increase in liver tumor burden. RNA sequencing of liver tumors and in vivo chromatin immunoprecipitation assays revealed a set of direct target genes that are...