A positive role for Myc in TGFbeta-induced Snail transcription and epithelial-to-mesenchymal transition.

摘要: Myc and transforming growth factor-beta (TGFbeta) signaling are mutually antagonistic, that is suppresses the activation of TGFbeta-induced genes, whereas TGFbeta represses c-myc transcription. Here, we report a positive role for in response, consisting induction an epithelial-to-mesenchymal transition (EMT) EMT-associated gene Snail. Knockdown either or effectors SMAD3/4 epithelial cells eliminated Snail by TGFbeta. Both SMAD complexes targeted promoter vivo, DNA binding occurring independent manner. was bound prior to treatment, required rapid upon induced On other hand, downregulation slower event, after induction. The response another cytokine, hepatocyte factor (HGF), also depended on SMAD4. Thus, contrary their antagonistic effects Cip1 INK4b, SMADs cooperate signal-dependent cells. Although serum-stimulated fibroblasts, it dispensable its these conditions, further illustrating action transcriptional regulation context-dependent. Our findings suggest may promoting EMT metastasis carcinomas.