The Transforming Growth Factor-Beta (TGF-beta) Signaling and its Role in Melanoma

Transforming growth factor-beta is a potent growth inhibitor for normal melanocytes. This function is lost in the course of tumorigenesis, since several melanoma cell lines are only slightly or not at all inhibited by TGF-beta. In melanoma, the transduction of antiproliferative signals by TGF-beta is often abolished, and the autocrine production of TGF-beta increased. By this way, several TGF-beta driven paracrine effects, such as extracellular matrix remodeling, neoangiogenesis, and immunosuppression induce local tumor growth and metastasis. The interaction of Smads, the major TGF-beta signaling proteins, with other signaling systems such as the mitogen-activated protein kinases, the SKI/SnoN proteins, and the protein kinase C family, possibly contributes to the escape of melanoma cells from TGF-beta growth control. Therefore, the clarification of the molecular interactions of the TGF-beta signaling pathway may further promote the development of new treatment concepts for melanoma.