Fig. 8

TGF-β signaling pathway regulated autophagy and EMT. Activation of TGF-β/Smad3 in epithelial cells triggers EMT, and the activation of TGF-β/Smad2 signaling pathway also stimulates EMT. Moreover, TGF-β1 induces EMT and cancer metastasis by directly targeting the cytoplasmic domain of E-cadherin (CDH1) and activating WNT/β-catenin signaling. Sometimes, TGF-β cooperates with synergistic factors to induce EMT, such as Ras. Once TGF-β is stimulated, EMT-related transcription factor STAT3 interacts with Ras, which induces SNAIL expression and promotes EMT. Naturally, TGF-β can stimulate the expression of mRNA transcripts of several autophagy-related genes, such as Beclin-1, Atg5, Atg7, and death-associated protein kinase (Dapk), and it induces accumulation of autophagosomes and activation of autophagic flux, which potentiates the induction of the autophagy. It is worthy that autophagy induces TGF-β1 expression and TGF-β1-dependent EMT via triggering cAMP/PKA/CREB signaling, which relies on autophagy-dependent phosphodiesterase 4A (PDE4A) degradation