TGF-beta signaling and epithelial-mesenchymal transition in cancer progression

Purpose of review TGF-beta acts as a potent driver of cancer progression through the induction of epithelial-mesenchymal transition (EMT), in which epithelial cells acquire mesenchymal phenotype, leading to enhanced motility and invasion. Recent reports highlight the fundamental roles of TGF-beta-induced EMT in multiple aspects of cancer progression. In this review, we focus on the novel insights into the roles of TGF-beta-induced EMT in cancer progression and the underlying mechanisms that enable TGF-beta to activate this epithelial plasticity response at transcription, translation, and posttranslational levels. Recent findings Smad-mediated transcription regulation is known to activate TGF-beta-induced EMT. More recently, novel mechanisms of epigenetic control, alternative splicing, miRNAs, translation control, and posttranslational modifications have been shown to play key roles in the control of EMT. In addition to initiating carcinoma cell invasion, TGF-beta-induced EMT can guide cancer cells to de-differentiate and gain cancer stem-cell-like properties. EMT also allows the generation of stromal cells that support and instruct cancer progression. Summary The differentiation plasticity of epithelial cells that mediates TGF-beta-induced EMT and reversion from mesenchymal to epithelial phenotype are increasingly seen as integral aspects of cancer progression that contribute to survival and dissemination of cancer cells. Further mechanistic insights under physiological conditions may lead to new therapeutic or prognostic strategies in cancer treatment.