What are the Mechanisms of TGF-β Signaling in Cancer?
TGF-β signals through a complex pathway involving TGF-β receptors (TGFBR1, TGFBR2) and intracellular SMAD proteins. Upon TGF-β binding, the receptors phosphorylate SMAD2 and SMAD3, which then form a complex with SMAD4. This complex translocates to the nucleus, where it regulates the transcription of target genes involved in cell cycle control, apoptosis, and EMT. Non-SMAD pathways, such as MAPK, PI3K/AKT, and Rho-like GTPase signaling, also contribute to the diverse effects of TGF-β in cancer.
