The Crosstalk of RAS with the TGF-β Family During Carcinoma Progression and its Implications for Targeted Cancer Therapy

Both RAS and transforming growth factor (TGF)-beta signaling cascades are central in tumorigenesis and show synergisms depending on tumor stage and tissue context. In this review we focus on the interaction of RAS subeffector proteins with signaling components of the TGF-beta family including those of TGF-beta s, activins and bone morphogenic proteins. Compelling evidence indicates that RAS signaling is essentially involved in the switch from tumor-suppressive to tumor-promoting functions of the TGF-beta family leading to enhanced cancer growth and metastatic dissemination of primary tumors. Thus, the interface of these signaling cascades is considered as a promising target for the development of novel cancer therapeutics. The current pharmacological anti-cancer concepts combating the molecular cooperation between RAS and TGF-beta family signaling during carcinoma progression are critically discussed.