Histone acetyltransferase MOF is involved in active transcription regulation through histone H4K16 acetylation. MOF is downexpressed in a number of human tumors, but biological function of MOF in endometrial cancer has not been fully defined. The estrogen receptor alpha (ER alpha) is a transcription factor that regulates estrogen-stimulated cell proliferation in hormone-responsive tumors. However, ER alpha expression is decreased in grade III ECa samples and high expression of ER alpha is associated with long disease-free survival in ECa. The molecular mechanism for these observations is still unclear. Here we demonstrate knockdown of MOF promotes ECa cell growth and proliferation in vitro and in vivo. Clinical evidence indicates that expression MOF is decreased and positively correlated with that of ER alpha in ECa tissues. Furthermore, MOF physically interacts with ERa and modulates ER alpha stability in ECa cells. In addition, MOF modulates expression of a subset of endogenous genes regulated by ER alpha. Taken together, our results define MOF as a potential tumor suppressor in ECa participates in maintenance of ER alpha protein stability and regulation of ER alpha action. (C) 2018 Elsevier Inc. All rights reserved.