Journal
CELL DEATH & DISEASE
Volume 14, Issue 7, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-023-05921-x
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Protein post-translational modification by SUMO regulates cellular responses including EMT and SnoN acts via sumoylation and interaction with HDAC1 and p300 to modulate EMT-related effects in breast cell organoids. HDAC1 suppresses, whereas p300 promotes, TGF-β-induced morphogenetic changes associated with EMT-related events. This study has implications in discovering new biomarkers and therapeutics for breast cancer and other epithelial cell-derived cancers.
Protein post-translational modification by the small ubiquitin-like modifier (SUMO) regulates the stability, subcellular localization, and interactions of protein substrates with consequences on cellular responses including epithelial-mesenchymal transition (EMT). Transforming growth factor beta (TGF & beta;) is a potent inducer of EMT with implications for cancer invasion and metastasis. The transcriptional coregulator SnoN suppresses TGF & beta;-induced EMT-associated responses in a sumoylation-dependent manner, but the underlying mechanisms have remained largely unknown. Here, we find that sumoylation promotes the interaction of SnoN with the epigenetic regulators histone deacetylase 1 (HDAC1) and histone acetylase p300 in epithelial cells. In gain and loss of function studies, HDAC1 suppresses, whereas p300 promotes, TGF & beta;-induced morphogenetic changes associated with EMT-related events in three-dimensional multicellular organoids derived from mammary epithelial cells or carcinomas. These findings suggest that sumoylated SnoN acts via the regulation of histone acetylation to modulate EMT-related effects in breast cell organoids. Our study may facilitate the discovery of new biomarkers and therapeutics in breast cancer and other epithelial cell-derived cancers.
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