Research Synopsis    |    Role of TGF-β in Human Malignancy    |    Lab Funding

Role of TGF-β in Human Malignancy

In normal, non-transformed cells, the TGF-β ligand acting through the TGF-β signaling pathway induces G1 cell cycle arrest to inhibit proliferation, induce differentiation, or promote apoptosis. During transformation into cancerous cells, various components of the TGF-β signaling pathway are mutated, making the cancer cells resistant to the effects of the TGF-β ligand. These TGF-β resistant cancer cells, which proliferate in an unregulated manner, as well as the surrounding stromal cells (fibroblasts) then increase their production of the TGF-β ligand. This TGF-β, by acting on the surrounding stromal cells, immune cells, and endothelial and smooth muscle cells, results in enhanced immunosuppression and angiogenesis, as well as increased invasiveness of the tumor, allowing for enhanced tumor invasion and metastasis. Some of the dichotomous effects of TGF-β also result from altered responsiveness of the tumor cells themselves, perhaps as they undergo epithelial to mesenchymal transition (EMT). Elucidating mechanisms for this dichotomous function remains an active area of investigation for the lab.