Research Interests: Activity of Angiogenic Factors in Cancer Development
Our laboratory is primarily interested in molecular and cellular mechanisms that mediate tumor vascularization and metastasis in a broad spectrum of human cancers, including breast cancer, colorectal cancer, and brain tumors. Tumor angiogenesis-the new vasculature formation from pre-existing blood vessels-is a fundamental process that allows tumor cells to proliferate and expand. These endothelial cell-lined vessels are initially triggered by a number of angiogenic factors derived from tumor cells and tumor-associated stromal cells such as VEGF, bFGF, and YKL-40. YKL-40, a secreted glycoprotein, was recently discovered to be intimately associated with breast cancer angiogenesis and development. We are investigating whether elevated levels of YKL-40 may serve as a new diagnostic and prognostic biomarker for breast cancer.
Tumor cells may also grow new blood vessels through a process called vasculogenic mimicry (VM), which also plays an important role in tumor vascularization and progression. For example, glioblastoma-one of the most aggressive brain tumors-uses this mechanism to develop a strong vascular phenotype. Moreover, glioblastoma stem-like cells (GSCs) are thought to mediate VM as well as angiogenesis. A model proposed for GSC differentiation into neural and vascular lineages is illustrated in the figure below. Identification of key molecules and their mechanisms that regulate tumor vascular formation and metastasis will offer immense value for cancer diagnosis, prognosis, and treatment.
Rays of Hope Center for Breast Cancer Research
Center of Excellence in Apoptosis Research
Francescone R, Scully S, Faibish M, Taylor S, Oh D, Moral L, Yan W, Bentley B, Shao R. The role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma. J Biol Chem. In press (2011).
Faibish M, Francescone R, Bentley B, Yan W, Shao R. A YKL-40 neutralizing antibody blocks tumor angiogenesis and progression: a potential therapeutic agent in cancers. Mol Cancer Ther. In press (2011).
Shao R, Scully S, Yan W, et al. The novel lupus antigen protein acheron enhances the development of human breast cancer. Inter J Cancer. In press (2011).
Yan W, Cao J, Arenas R, Bentley B, Shao R. GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition. J Biol Chem. 2010;285:14042-14051.
Shao R, Hamel K, Petersen L, et al. YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene. 2009;28:4456-4468.
Apopa P, Qian Y, Shao R, et al. Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling. Particle Fibre Toxicol. 2009;6:1-14.
Khimji A, Shao R, Rockey DC. Divergent transforming growth factor-β signaling in hepatic stellate cells after liver injury. Am J Pathol. 2008;173:716-727.
Yan W, Bentley B, Shao R. Distinct angiogenic mediators are required for bFGF and VEGF-induced angiogenesis: the role of cytoplasmic tyrosine kinase c-Abl in tumor angiogenesis. Mol Biol Cell. 2008;19:2278-2288.
Yan W, Shao R. Transduction of a mesenchyme-specific gene periostin into 293T cells induces cell invasive activity through epithelial-mesenchymal transformation. J Biol Chem. 2006;281:19700-19708.
Shao R, Guo X. Human microvascular endothelial cells immortalized with hTERT: a model for the study of in vitro angiogenesis. Biochem Biophys Res Commun. 2004;321:788-794.
Bao S, Ouyang G, Bai X, Zhi H, Ma C, Liu M, Shao R, et al. Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell. 2004;5:329-339.
Shao R, Bao S, Bai X, et al. Acquired expression of periostin by breast cancers promotes tumor progression via enhancement of angiogenesis. Mol Cell Biol. 2004;24:3992-4003.
Shao R, Shi Z, Gotwals PJ, Koteliansky VE, Rockey DC. Cell and molecular regulation of endothelin-1 production during hepatic wound healing. Mol Biol Cell. 2003;14:2327-2341.
Hubbert C, Guardiola A, Shao R, et al. HDAC6 is a microtubule-associated deacetylase. Nature. 2002;417:455-458.
Shao R, Rockey DC. Effects of endothelins on hepatic stellate cell synthesis of endothelin-1 during hepatic wound healing. J Cell Physiol. 2002;191:342-350.
Yu Q, Shao R, Qian HS, George SE, Rockey DC. Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. J Clin Invest. 2000;105:741-748.
Shao R, Yan W, Rockey DC. Endothelin production is regulated by endothelin converting enzyme-1 in hepatic wound healing. J Biol Chem. 1999;274:3228-3234.
Symposium platform presentation at the American Association for the Study of Liver Diseases 1999
Symposium platform presentation at the Era of Hope, DOD Breast Cancer Research Program meeting 2002