EMT Induction

Many pathways that induce epithelial to mesenchymal transition (EMT) activate intracellular signal transduction cascades and modulate the expression of epithelial and mesenchymal cell-specific genes. For example, TGF-beta, Wnt, and receptor tyrosine kinase signaling cascades result in the transcription and accumulation of transcription factors such as Snail, Twist, Slug, and ZEB1, which modulate gene expression. For example during physiological processes such as wound healing, EGF can induce EMT and promote cell migration and reepithelialization. During both normal embryonic development and pathological conditions, such as fibrosis and cancer progression, TGF-beta signaling activates the transcription factor Snail, represses E-Cadherin expression, and induces EMT. In addition, hypoxia and MMP-induced Rac1b expression cause an increase in cellular reactive oxygen species, which results in the accumulation of Snail and progression of EMT. Increasing evidence suggests that numerous signaling pathways interact to induce or inhibit EMT depending on specific cellular contexts. For instance, BMP signaling activates EMT in neural crest cells. In contrast, BMP-7 is thought to negatively regulate EMT during fibrosis and promote mesenchymal to epithelial transition (MET) in the developing kidney.