NIH P01: Prostate Cancer Bone Metastasis: Biology and Targeting
Models for Predicting PCa Progression (MPPP)
Wen-Chin Huang, Ph.D.
Assistant
Professor
Molecular Urology and Therapeutics Program
Department of Urology
Contact Information
Department of Urology
Emory University School of Medicine
Clinic B, Suite 5105
1365 Clifton Road, N.E.
Atlanta, GA 30322
Phone: 404-778-3683
Fax: 404-778-3965
Email: whuang3@emory.edu
Education
PhD, National Taiwan University,
Taipei, Taiwan, 2000, Biochemistry/Molecular Biology
M.S., National Taiwan University, Taipei, Taiwan, 1992, Biochemistry
B.S., National Chung-Hsing University, Taichung, Taiwan, 1990, Food Science
Research Interests
The major areas of Dr. Huang's research focus on signaling transduction, gene promoter study and molecular targeting. We identified a small protein, beta 2-microglobulin, which is well-known as a housekeeping gene product. However, it plays a critical role in promoting human prostate cancer cell growth, progression and bone metastasis (osteomimicry) through a cAMP/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signaling pathway. He has demonstrated that targeting beta 2-microglobulin and its related downstream signaling pathways by using sequence-specific beta 2-microglobulin siRNA (from intracellular resource) or anti-beta 2-microglobulin antibody (from extracellular resource) significantly inhibit prostate cancer growth in vitro and in vivo, and dramatically decrease expression of androgen receptor, which is a survival and nuclear transcription factor for prostate cancer, and prostate-specific antigen, which is used as a biomarker for diagnosis of prostate cancer, in prostate cancer cells. Most importantly, anti-beta 2-microglobulin antibody selectively kills prostate cancer cells but does not affect normal prostatic cells. With these promising findings, Dr. Huang is interested in exploring the biological activities of beta 2-microglobulin siRNA and anti-beta 2-microglobulin antibody as gene and immunologic therapies in depth, in the hope that these may allow us to develop attractive and safe anti-prostate tumor drugs for the potential clinical application.
Selected Publications
Huang, W.C., Xie, Z., Konaka, K., Sodek, J., Zhau, H.Z., and Chung, L.W. Human osteocalcin and bone sialoprotein mediating osteomimicry of prostate cancer cells: Role of cAMP-dependent protein kinase A signaling pathway. Cancer Res, 65: 2303-2313, 2005.
Huang, W.C. Odero-Marah, V., Chung, L.W. Bone Metastasis: Experimental and Clinical Aspects: Biologic and therapeutic implications of osteomimicry and epithelial-mesenchymal transition in prostate Cancer. Humana Press, Totowa, NJ. p. 75-86, 2005.
Chung, L.W., Huang, W.C., Sung, S.Y., Wu, D., Odero-Marah, V., Nomura, T., Shigemura, K., Miyagi, T., Seo, S., Shi, C., Molitierno, J., Elmore, J., Anderson, C., Isotani, S., Edlund, M., Hsich, C.L., Wang, R., Shehata, B., and Zhau, H.E. Stromal-epithelial interaction in prostate cancer progression. Clin Genitourin Cancer, 5: 162-170, 2006.
Huang, W.C., Wu, D., Xie, Z., Zhau, H.E., Nomura, T., Zayzafoon, M., Pohl, J., Hsieh, C.L., Weitzmann, M.N., Farach-Carson, M.C., and Chung, L.W. beta 2-Microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Res, 66: 9108-9116, 2006.
Nomura, T., Huang, W.C., Zhau, H.E., Wu, D., Xie, Z., Mimata, H., Zayzafoon, M., Young, A.N., Marshall F.F., Weitzmann, M.N., and Chung, L.W. beta 2-Microglobulin promotes the growth of human renal cell carcinoma through the activation of the protein kinase A, cyclic AMP-responsive element-binding protein, and vascular endothelial growth factor axis. Clin Cancer Res, 12: 7294-7305, 2006.
Wu, D, Zhau, H.E., Huang, W.C., Iqbal, S. Habib, F., Sartor, O., Cvitananovic, L., Marshall, F., Xu, W., and Chung, L.W. cAMP-response element-binding protein regulates vascular endothelial growth factor expression: implication in human prostate cancer bone metastasis. Oncogene, 26: 5070-5077, 2007.
Nomura, T., Huang, W.C., Seo, S., Zhau, H.E., Mimata, H., and Chung, L.W. Targeting beta 2-microglobulin mediated signaling as a novel therapeutic approach for human renal cell carcinoma. J Urol, 178: 292-300, 2007.
Huang W-C, Havel JJ, Zhau HE, Qian W-P, Lue H-W, Chu C-Y, Nomura T, and Chung LWK. beta 2-Microglobulin signaling blockade inhibited androgen receptor axis and caused apoptosis in human prostate cancer cells. Clinical Cancer Res. 14(17):5341-7.
Zhau HE, Odero-Marah VA, Lue H-W, Nomura T, Wang R, Chu G, Liu Z-R, Zhou BP, Huang W-C, and Chung LWK. Epithelial to Mesenchymal Transition (EMT) in Human Prostate Cancer: Lessons Learned from ARCaP Model. Clinical and Experimental Metastasis 25(6):601-10.