Ray-Chang WuAssociate Professor of Biochemistry and Molecular Medicine
Office Phone: 202-994-1891
Department: Biochemistry and Molecular Medicine
- BS, National Yang-ming University, 1989
- PhD, University of Southern California, 1999
Steroid receptor coactivator 3 (SRC-3/AIB1/ACTR/RAC3/p/CIP), a member of the p160 family of coactivators, is a bona fide oncogene involved in many human cancers. Development of cancer is a multistep process that requires changes of intrinsic cellular functions and interaction of cancerous cells with the tumor microenvironment. Cancer cells are “addicted” to SRC-3/AIB1 oncogene as over-expression of SRC-3/AIB1 is found in many human cancers and is associated with cancer initiation, metastasis and resistance to chemotherapy. However, the reason why cancer cells are addicted to SRC-3/AIB1 oncogene remains unclear. Therefore, understanding the molecular mechanisms underpinning the oncogenic activity of SRC-3/AIB1 is critical for improving anti-cancer therapy. To fully understand the mechanisms by which SRC-3/AIB1 contributes to the development and progression of human cancer, we had identified several molecular targets of SRC-3/AIB1 by functional rescue experiments and gene expression profiling. Currently, we are focusing on understanding the function and importance of these molecular targets of SRC-3/AIB1 in tumorigenesis and on elucidating the underlying mechanisms at the molecular and cellular levels. Since most current targeted cancer therapies are designed to block a single pathway, cancers often become resistant by switching to another growth pathway. In contrast, cancer cells are less likely to survive loss of SRC-3/AIB1 oncogene because of this “addiction”. Since SRC-3/AIB1 is frequently over-expressed in a wide variety of cancers, our study also argues that cancer drugs targeting SRC-3/AIB1 is likely to impact more than one type of cancer.
View publications by this faculty member from January 1, 2013 - present
Mei-Yi Wu, Junjiang Fu, Xiuli Xiao, Jingbo Wu, and Ray-Chang Wu. MiR-34a Regulates Therapy Resistance by Targeting HDAC1 and HDAC7 in Breast Cancer. Cancer Letters, 2014 (in press).
Yi P., Xia W, Wu R.C., Lonard D.M., Hung M.C. and O'Malley B.W. (2013) SRC-3 coactivator regulates cell resistance to cytotoxic stress via TRAF4-mediated p53 de-stabilization. Genes & Development. (in press)
Wu R.C. *, Jiang M., Beaudet A.L., and Wu M.Y. (2013) ARID4A and ARID4B regulate male fertility, a functional link to the AR and RB pathways. Proc Natl Acad Sci U S A. (in press) *corresponding author
Wu, M.Y., Fu, J., Xu, J., O’Malley, B.W., and Wu R.C. Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor. Cell Research. 2012, in press.
Wu, M.Y, Jiang, M., Zhai, X., Beaudet, A., Wu, R.C. An Unexpected Function of the Prader-Willi Syndrome Imprinting Center in Maternal Imprinting in Mice. PLoS One, in press. 2012.
Liu Y, Tong Z, Li T, Chen Q, Zhuo L, Li Q, Wu RC, Yu C. Hepatitis B virus X protein stabilizes AIB1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness. Hepatology. 2012 Apr 2. doi: 10.1002/hep.25751. [Epub ahead of print] PMID: 22473901.
Sarachana T, Xu M, Wu R.C., Hu VW. Sex hormones in autism: androgens and estrogens differentially and reciprocally regulate RORA, a novel candidate gene for autism. PLoS One. 2011 Feb 16;6(2):e17116.
York B., Yu C., Sagen J.V., Liu Z., Nikolai B.C., Wu R.C., Finegold M., Xu J., O'Malley B.W. Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11122-7. PMID: 20534466
Xu J., Wu R.C., O'Malley B.W. (2009) Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat. Rev. Cancer, 9(9):615-30. PMID: 19701241
Li C., Wu R.C., Amazit L., Tsai S.Y., Tsai M.-J., and O’Malley B.W. (2007) Specific amino acid residues in the bHLH domain of SRC-3 are essential for its nuclear localization and proteasome-dependant turnover. Mol. Cell. Biol., 27(4):1296-308. PMID: 17158932
Wu R.C., Feng Q., Lonard D.M. and O’Malley B.W. (2007) SRC-3 coactivator functional lifetime is regulated by a phospho-dependent ubiquitin time clock. Cell, 129(6):1125-40. PMID: 17574025
Wu R.C., Smith C.L., O’Malley B.W. Transcriptional regulation by steroid receptor coactivator phosphorylation. Endocrine Reviews. 2005 26 (3): 393-399. PMID: 15814849
Zheng F.F., Wu R.C., Smith C.L. and O’Malley B.W. Rapid estrogen-induced phosphorylation of SRC-3 coactivator occurs in an extranuclear complex containing estrogen receptor. Mol. Cell. Biol. 2005 Sep;25(18):8273-84. PMID: 16135815
Wu R.C., Qin J., Yi P., Wong J., Tsai S. Y., Tsai M.-J., and O’Malley B.W. (2004) Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic responses to multiple cellular signaling pathways. Mol. Cell, 24;15(6):937-49. PMID: 15383283
Wu R.C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., O'Malley B.W. (2002) Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase. Mol. Cell. Biol., 22(10):3549-61. PMID: 11971985
Additional publications published before January 1, 2013 may be available within Himmelfarb Library's database.
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the healthcare related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.