Research

TGF-ß signal transduction, transcriptional regulation, cell cycle control, cancer

Transforming growth factor-ß (TGF-ß) and related polypeptides, including activins and bone morphogenetic proteins (BMPs), constitute the largest cytokine family, possessing fascinating features. They are multifunctional, regulating essentially all aspects of cellular processes. For example, TGF-ß potently inhibits cell proliferation by causing cell cycle arrest at the G1 phase. TGF-ß also regulates cell differentiation, adhesion, motility and apoptosis. TGF-ß family members are evolutionarily conserved and play an essential role in the development and homeostasis of virtually every tissue in organisms ranging from fruit flies to humans. Alterations of the TGF-ß signaling pathways are associated with human disorders, such as cancer and fibrosis.

TGF-ß signals through transmembrane serine/threonine kinase receptors. It binds and brings together two classes of receptors, the type I and type II receptors. The TGF-ß type II receptor is constitutively active. It transphosphorylates the type I receptor, which then plays a major role in specifying downstream events, leading to various biological responses.

Smad proteins transduce the TGF-ß signal from the cell surface to the nucleus. Smads are directly phosphorylated by the TGF-ß family receptor kinases upon ligand stimulation. Following phosphorylation, Smads form heteromeric complexes, accumulate in the nucleus, and regulate transcription of a variety of target genes, such as cell cycle regulators.

TGF-ß is a potent tumor suppressor at early stages of tumorigenesis. At late stages, TGF-ß promotes tumor progression and metastasis.

Our research covers TGF-ß/Smad signal transduction, transcriptional regulation, cell cycle control, cancer (especially breast cancer), and fibrosis.