Transforming growth factor beta (TGFβ) is a pleiotropic growth factor. Under normal physiological conditions, TGFβ maintains homeostasis in mammalian tissues by restraining the growth of cells and stimulating apoptosis. However, the role of TGFβ signaling in the carcinogenesis is complex. TGFβ acts as a tumor suppressor in the early stages of disease and as a tumor promoter in its later stages where cancer cells have been relieved from TGFβ growth controls. Overproduction of TGFβ by cancer cells lead to a local fibrotic and immune-suppressive microenvironment that fosters tumor growth and correlates with invasive and metastatic behavior of the cancer cells. Here, we present an overview of the complex biology of the TGFβ family, and we discuss the roles of TGFβ signaling in carcinogenesis and how this knowledge is being leveraged to develop TGFβ inhibition therapies against the tumor.
Keywords: Angiogenesis; Cancer-associated fibroblast; Epithelial-mesenchymal transition; Extracellular matrix; Immune cells; Invasion; Matrix remodeling; Metastasis; Metastatic niche; Microenvironment; TGFβ; TGFβ pathway inhibitors; TGFβR; Targeted therapy; Tumor.