Laboratory of Surgical Oncology
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Assistant Investigator, The Feinstein Institute for Medical Research
Assistant Professor, Department of Surgery
North Shore-LIJ Health System
350 Community Drive, Manhasset, NY 11030
Phone: (516) 562-2835
Fax: (516) 562-1022
wlyang@nshs.edu
Research Overview:
Colorectal cancer is one of the most commonly diagnosed malignancies in the United States and currently ranks as the second leading cause of cancer-related death. More than 50% of colorectal cancer deaths are due to the spread (or metastasis) from colon to the liver. Metastasis of cancer cells is the cumulative result of a complex series of processes, which consist of proliferation of the primary tumor, the release of tumor cells from the primary site into the blood vessels, the survival of cancer cells in the blood vessels, extravasation and tumor growth at the distant organs. So far, no effective treatment exists for metastatic tumors. The long term goal of our laboratory is to understand how primary cancer cells turn into aggressive metastatic cells, which will lead to develop therapeutic strategies for preventing tumor spreading. Recently, we have identified that bone morphogenetic protein 4 (BMP-4) levels are markedly increased in the late-stage of human colorectal tumors. BMPs are members of the TGF-ß superfamily. More than 20 different BMP isoforms have been identified. BMPs exert their activity through binding receptor complex to activate the translocation of Smad complex into the nucleus, which results in suppression or activation of target gene expression. The elevated BMP-4 levels in colorectal cancer cells results in changing cell behaviors to become more invasive. We are currently investigating what other invasive phenotypes are induced by BMP-4 singling and elucidating molecular mechanisms by which BMP-4 signaling governs the malignancy of colorectal cancer cells for progression.
Cancer prevention is another research interest in our laboratory. It has been recognized that people with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer. Release of inflammatory cytokines may contribute such link. Unlike other cytokines, macrophage migration inhibitory factor (MIF) is regularly produced in the intestine and further elevated in patients with IBD or colorectal cancer. We are studying whether MIF is required for developing colorectal cancer associated with chronic inflammation. We have identified several dietary active components (e.g. curcumin, quercetin, resveratrol, and butyrate) can decrease MIF levels in colorectal cancer cells, which leads to postulate MIF as a target of chemo-prevention for IBD-associated colorectal cancer.
Lab Member:
Name: Haiyun Deng, PhD
Position: Research Associate
Research: Works with human colon cancer cells.
E-mail: hdenge@nshs.edu
Select Publications:
Deng H, Ravikumar TS and Yang W-L. 2009. Overexpression of bone morphogenetic protein 4 enhances the invasiveness of Smad4-deficient human colorectal cancer cells. Cancer Lett. 281:220-231.
Wang SM and Yang W-L. 2009. Circulating hormone adrenomedullin and its binding protein protect neural cells from hypoxia-induced apoptosis. Biochim. Biophys. Acta. 1790:361-367.
Miksa M, Amin D, Wu R, Jacob A, Zhou M, Dong W, Yang W-L, Ravikumar TS and Wang, P. 2008. Maturation-induced down-regulation of MFG-E8 impairs apoptotic cell clearance and enhances endotoxin response. Int. J. Mol. Med. 22:743-748.
Makizumi R, Yang W-L, Owen RP, Sharma RR and Ravikumar TS. 2008. Alteration of drug sensitivity in human colon cancer cells after exposure to heat: Implications for liver metastasis therapy using RFA and chemotherapy. Int. J. Clin. Exp. Med. 1:117-129.
Deng H, Ravikumar TS and Yang W-L. 2007. Bone morphogenetic protein-4 inhibits heat-induced apoptosis by modulating MAPK pathways in human colon cancer HCT116 cells. Cancer Lett. 256:207-217.
Deng H, Makizumi R, Ravikumar TS, Dong H, Yang W and Yang W-L. 2007. Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. Exp. Cell Res. 313:1033-1044.
Sharma RR, Ravikumar TS, Raimo D and Yang W-L. 2005. Induction of p21WAF1 expression protects HT29 colon cancer cells from apoptosis induced by cryo-injury. Ann. Surg. Oncol. 12:743-752.
Yang W-L, Nair DG, Makizumi R, Gallos G, Ye X, Sharma RR and Ravikumar TS. 2004. HSP70 is induced in mouse human colon tumor xenografts after sublethal radiofrequency ablation. Ann. Surg. Oncol. 11:399-406.
Yang W-L, Yang-Biggs G, Wu Y, Ye X, Gallos G, Owen RP and Ravikumar TS. 2003. Development of resistance by combination of heat treatment with cisplatin and hydroxyurea in FaDu squamous carcinoma cells. J. Surg. Res. 111:143-151.