Figure 2.

Negative modulation of EMT by sirtuins. SIRT1 can inhibit the TGF-β signaling pathway by deacetylating Smad4. This leads to decreased MMP7 transcription and expression, with consequent reduced E-cadherin degradation. Being bound to E-cadherin, β-catenin cannot shuttle to the nucleus, with subsequent lack of its prosurvival, EMT-inducing effects. Similarly, SIRT2 downregulates β-catenin, while promoting the expression of E-cadherin. By inhibiting the mitochondrial glutamine metabolism, SIRT4 suppresses EMT.