The role of transforming growth factor-beta (TGF-beta) superfamily signaling pathways in cancer biology.
Our laboratory focuses on the role of transforming growth factor-beta (TGF-beta) superfamily signaling pathways in cancer biology. The TGF-beta signaling pathway functions as both a tumor-suppressor and as tumor promoter during carcinogenesis. This dichotomy of TGF-beta function remains a fundamental problem in the field both in terms of understanding the mechanism of action of the TGF-beta pathway, and directly impacting our ability to target this pathway for the chemoprevention or treatment of human cancers. Resistance to the tumor suppressor effects of TGF-beta is also a common feature of epithelial-derived human cancers, however, mechanisms for TGF-beta resistance remain undefined in the majority of cases. The laboratory is currently focused on elucidating mechanisms for TGF-beta resistance and for the dichotomous function of TGF-beta in human breast, colon, pancreatic and renal cell cancers using a multidisciplinary approach. TGF-beta and the TGF-beta signaling pathway also have an important role in vascular biology. Indeed, mutations in two endothelial specific TGF-beta receptors, endoglin and ALK-1, are responsible for the human vascular disease, hereditary hemorrhagic telangiectasia (HHT), and mice which lack expression of these receptors are embryonic lethal due to defects in angiogenesis. Studies are currently underway to elucidate the signal transduction pathway downstream from these receptors and to establish their role in regulating tumor-induced angiogenesis. The ultimate goal of these studies is the ability to target the TGF-beta pathway for the chemoprevention or treatment of human cancers.