SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis

摘要: The epithelial-to-mesenchymal transition (EMT) is a crucial program for the invasion and metastasis of epithelial tumors that involves loss cell–cell adhesion increased cell mobility; however, mechanisms underlying this are not fully elucidated. Here, we propose novel mechanism through which nicotinamide adenine dinucleotide-dependent histone deacetylase SIRT1 regulates EMT in prostate cancer cells cooperation with inducing transcription factor ZEB1. We found forced expression non-transformed PZ-HPV-7 disrupts morphology concomitant decreased marker, E-cadherin, mesenchymal markers. In contrast, silencing metastatic tumor restores induces shift toward an E-cadherin also has physiologically relevant role endogenous induced by EGF signaling cells. regulation modulation of, with, Specifically, show reduces ZEB1 recruited to proximal promoter deacetylate H3 reduce binding RNA polymerase II, ultimately suppressing transcription. thus identify necessary SIRT1-mediated EMT. Finally, reduction decreases migration vitro vivo immunodeficient mice, largely independent any general effects on growth survival. therefore as positive regulator our findings implicate overexpressed potential therapeutic target reverse prevent progression.