Epithelial-mesenchymal transition is regulated at post-transcriptional levels by transforming growth factor-β...

Transforming growth factor (TGF)-β acts as a tumor suppressor during cancer initiation, but as a tumor promoter during tumor progression. It has become increasingly clear that TGF-β plays fundamental roles in multiple steps of tumor progression, including epithelial-mesenchymal transition (EMT). The EMT, first described by developmental biologists at the beginning of the 1980s, plays crucial roles in appropriate embryonic development, but also functions in adults during wound healing, organ fibrosis, and tumor progression. During EMT, epithelial cells lose their epithelial polarity and acquire mesenchymal phenotypes, endowing them with migratory and invasive properties. Many secreted polypeptides are implicated in this process, and act in a sequential or cooperative manner. TGF-β induces EMT by propagating intracellular signaling pathways and activating transcriptional factors. Here, I discuss new insights into the molecular mechanisms underlying induction of EMT by TGF-β in cooperation with Ras or growth factors, along with the signals that induce EMT through transcriptional and post-transcriptional regulation.