Suppression of TGF?-induced epithelial-mesenchymal transition like phenotype by a PIAS1 regulated sumoylation pathway in NMuMG epithelial cells.
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ABSTRACT: Epithelial-mesenchymal-transition (EMT) is a fundamental cellular process that is critical for normal development and tumor metastasis. The transforming growth factor beta (TGF?) is a potent inducer of EMT like effects, but the mechanisms that regulate TGF?-induced EMT remain incompletely understood. Using the widely employed NMuMG mammary epithelial cells as a model to study TGF?-induced EMT, we report that TGF? downregulates the levels of the SUMO E3 ligase PIAS1 in cells undergoing EMT. Gain and loss of function analyses indicate that PIAS1 acts in a SUMO ligase dependent manner to suppress the ability of TGF? to induce EMT in these cells. We also find that TGF? inhibits sumoylation of the PIAS1 substrate SnoN, a transcriptional regulator that antagonizes TGF?-induced EMT. Accordingly, loss of function mutations of SnoN sumoylation impair the ability of SnoN to inhibit TGF?-induced EMT in NMuMG cells. Collectively, our findings suggest that PIAS1 is a novel negative regulator of EMT and reveal that inhibition of the PIAS1-SnoN sumoylation pathway represents a key mechanism by which TGF? induces EMT, with important implications in normal development and tumor metastasis.
SUBMITTER: Netherton SJ
PROVIDER: S-EPMC2980481 | biostudies-literature | 2010 Nov
REPOSITORIES: biostudies-literature
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