RT Journal Article ID 26c762a645460d68 A1 Kaplun, Alexander A1 Dzinic, Sijana A1 Bernardo, M. Margarida A1 Sheng, Shijie T1 Tumor Suppressor Maspin as a Rheostat in HDAC Regulation to Achieve the Fine-Tuning of Epithelial Homeostasis JF Critical Reviews™ in Eukaryotic Gene Expression JO CRE YR 2012 FD 2012-10-31 VO 22 IS 3 SP 249 OP 258 K1 maspin K1 HDAC K1 tumor suppressor K1 re-differentiation K1 epigenetic regulation K1 E-cadherin K1 MEF2 K1 Nanog K1 TGFβ K1 Abl AB Maspin, a class II tumor suppressor, is often downregulated during tumor progression and its depletion from the nucleus is associated with poor prognosis. Recently, we reported that reintroduction of maspin is sufficient for redifferentiation of prostate cancer cells to epithelial phenotype, a reversal of epithelial-to-mesenchymal transition. We have linked this effect of maspin with its ability to directly inhibit HDAC1, thereby influencing the acetylation state of transcription factors and other proteins. Maspin overexpression leads to changes in the expression level of a large number of proteins and these changes are often microenvironment specific. In this review, we summarize the epigenetic effects of maspin and provide comprehensive bioinformatic analysis of microarray-derived gene expression changes caused by maspin in different microenvironments. The analysis was performed on multiple levels, including identification of statistically enriched gene ontology groups, detection of overreprepresented transcription factors binding sites in promoters of differentially expressed genes, followed by searching for key nodes of regulatory networks controlling these transcription factors. The results are consistent with our hypothesis that maspin serves as an endogenous regulator of HDAC activity and suggest that the effect of maspin is primarily mediated by TGFβ, β-catenin/E-cadherin pathways, and network key nodes such as Abl kinase, p62, IL1, and caspases 6 and 8. PB Begell House LK https://www.dl.begellhouse.com/journals/6dbf508d3b17c437,32f018b6385e752a,26c762a645460d68.html