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)-β 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-β family including those of TGF-βs, 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-β 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-β family signaling during carcinoma progression are critically discussed.
Grusch
Michael
M
Department of Medicine I, Division, Institute of Cancer Research, Medical University of Vienna, Borschke-Gasse 8a, A-1090 Vienna, Austria.
Petz
Michaela
M
Metzner
Thomas
T
Oztürk
Deniz
D
Schneller
Doris
D
Mikulits
Wolfgang
W
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta; D018631:ras Proteins