Molecular pathways: targeting the TGF-β pathway for cancer therapy.
TGF-β is a ubiquitous cytokine that plays an active role in many cellular processes. Nearly every cell type has the ability to secrete TGF-β, as well as the ability to respond to TGF-β via the presence of TGF-β receptors on the cell surface. Consequently, gain or loss of function of the TGF-β pathway and its components are known to lead to a variety of diseases, including cancer. In epithelial cells, TGF-β functions as a tumor suppressor, where it inhibits proliferation, induces apoptosis, and mediates differentiation. Conversely, in other contexts, TGF-β promotes tumor progression through increasing tumor cell invasion and metastasis. Thus, TGF-β can have opposing roles, likely dependent, in part, on whether the cancer is early or late stage. The effects of TGF-β on tumor suppression and promotion are not limited to the tumor cell itself; rather, these effects can also be mediated through the stroma and the immune system. The dichotomous role of TGF-β in cancer highlights our need to understand the contextual effects of this cytokine to better guide patient selection for the use of anti-TGF-β therapies currently in clinical trials.
Program in Molecular Biology, Medical Scientist Training Program, Departments of Pharmacology and Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Anna L
AL
Smith
Tyler P
TP
Robin
Heide L
HL
Ford
D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D004847:Epithelial Cells; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D053858:Metabolic Networks and Pathways; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D057170:Translational Research, Biomedical
D016212:Transforming Growth Factor beta