Regulation of epithelial-mesenchymal transition by protein lysine acetylation

Abstract

The epithelial-mesenchymal transition (EMT) is a vital driver of tumor progression. It is a well-known and complex trans-differentiation process in which epithelial cells undergo morphogenetic changes with loss of apical-basal polarity, but acquire spindle-shaped mesenchymal phenotypes. Lysine acetylation is a type of protein modification that favors reversibly altering the structure and function of target molecules via the modulation of lysine acetyltransferases (KATs), as well as lysine deacetylases (KDACs). To date, research has found that histones and non-histone proteins can be acetylated to facilitate EMT. Interestingly, histone acetylation is a type of epigenetic regulation that is capable of modulating the acetylation levels of distinct histones at the promoters of EMT-related markers, EMT-inducing transcription factors (EMT-TFs), and EMT-related long non-coding RNAs to control EMT. However, non-histone acetylation is a post-translational modification, and its effect on EMT mainly relies on modulating the acetylation of EMT marker proteins, EMT-TFs, and EMT-related signal transduction molecules. In addition, several inhibitors against KATs and KDACs have been developed, some of which can suppress the development of different cancers by targeting EMT. In this review, we discuss the complex biological roles and molecular mechanisms underlying histone acetylation and non-histone protein acetylation in the control of EMT, highlighting lysine acetylation as potential strategy for the treatment of cancer through the regulation of EMT.

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

“…The abnormal expression of HDASs is tightly linked with several cancers, and their inhibitors have been applied in the clinic to treat several cancers (Patel et al, 2022). Moreover, histone modification impacts the process of epithelial-mesenchymal transition (EMT), and histone acetylation can modulate the acetylation levels of distinct histones at the promoters of EMT-related markers, EMT-inducing transcription factors, and EMT-related long noncoding RNAs to control EMT (Kong et al, 2022). Histone modification function also emerges in the carcinogenesis of cervical cancer.…”

Continuous genetic monitoring of transient mesenchymal gene activities in distal tubule and collecting duct epithelial cells during renal fibrosis

“…Zeb (Zeb1 and Zeb2), one of the EMT-TF families, is a key regulator of epithelial gene repression and mesenchymal gene upregulation during the EMT process. 26,28,65 To detect if the key EMT-TF Zeb1 was expressed in E-Cad + and EpCAM + ECs during renal fibrosis, we treated 8-week-old Zeb1-EMTracer mice (Figure 3A) with tamoxifen, performed UUO surgery or sham operation after 2 weeks of washout, and harvested renal tissues following 7, 10, and 15 days of UUO (Figure 3D). Whole-mount fluorescence view of the kidneys showed that there was no detectable tdTomato signal at 7, 10, and 15 days after UUO (Figure 3E,H).…”

“…They simultaneously undergo changes in phenotype and cell morphology, cytoskeletal remodeling, and detachment from the tubular basement membrane (TBM), express EMT-TFs and other mesenchymal markers (such as αSMA, vimentin, and N-cadherin), and acquire a mesenchymal or myofibroblastic characteristic, motility properties, and collagen production capacities. 2,5,23,[25][26][27][28] The studies on EMT in kidney fibrosis were initiated by Eric Neilson's group. In 1995, Struz and colleagues identified fibroblast-specific protein 1 (FSP1, also known as S100A4 or MTS-1) as a highly specific marker of fibroblast.…”

Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

“…The ability of HATs to manipulate chromatin structure and epigenetic framework is imperative for cell maintenance and survival 73–75 . It plays multiple functional roles in regulating proliferation, apoptosis, epithelial mesenchymal transition (EMT), and CSC in a variety of human cancers 76–79 . To classify the functions of hundreds of proteins that regulate chromatin, enzymes that regulate PTMs are subdivided into “writers,” “erasers,” “readers,” and “movers.” 76 The identification of mammalian HATs (writers) and HDACs (erasers), bromodomain‐containing domains (readers), and HDACIs have laid the foundation for in‐depth studies of histone acetylation modifications 80,81 .…”