Fig. 9: Schematic model of the TGF-β/SMAD4/14-3-3σ/TFEB signaling pathway. | Cell Death & Disease

Fig. 9: Schematic model of the TGF-β/SMAD4/14-3-3σ/TFEB signaling pathway.

From: TGF-β/SMAD4/14-3-3σ/TFEB axis promotes mesenchymal-epithelial transition and inhibits autophagy in colorectal cancer

Fig. 9: Schematic model of the TGF-β/SMAD4/14-3-3σ/TFEB signaling pathway.The alternative text for this image may have been generated using AI.

The scheme summarizes the findings of this study. Activation of SMAD4 by TGF-β results in its nuclear translocation and binding of SBEs within the 14-3-3σ promoter and transcriptional activation of 14-3-3σ. The resulting increase of cytoplasmic 14-3-3σ protein levels promotes sequestration of the transcription factor TFEB via binding to the phosphorylated Ser211 motif within TFEB. Therefore, the TFEB-/CLEAR-motif mediated transcription, which mediates autophagy and EMT, is inhibited, resulting in reduced invasion and migration, and presumably decreased survival of CRC cells. SBE SMAD-binding elements, CLEAR coordinated lysosomal and autophagic regulation.

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