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Over two decades of research on cancer-associated epithelial-mesenchymal transition (EMT) led us to ascertain the occurrence of transitional intermediate states (collectively referred to as the EMT spectrum). Among the molecular factors that drive EMT, SNAI1 plays an indispensable role in regulating other core transcription factors, and this regulation is highly context-dependent. However, molecular investigation on this context-dependent regulation is still lacking. Using two ovarian cancer cell lines, we show that SNAI1 regulation on other core EMT-TFs switches from a repressive control in highly epithelial cells to an activation signaling in intermediate epithelial cells. Upon further scrutiny, we identify that the expression of early epithelial genes PERP and ERBB3 are differentially regulated in SNAI1-induced sequential EMT changes. Mechanistically, we show that changes in PERP and ERBB3 transcript levels could be correlated to the selective enrichment loss of RAD21, a cohesin component, at the distal enhancer sites of PERP and ERBB3, which precedes that of the proximal promoter-associated sites. Furthermore, the RAD21 enrichment at the distal enhancer sites is dependent on GRHL2 expression. In a nutshell, the alteration of GRHL2-associated RAD21 enrichment in epithelial genes is crucial to redefine the transition of cellular states along the EMT spectrum. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transcription factors are commonly deregulated in various cancers. Here, we evaluated role of ELF3 in pathogenesis of bladder carcinoma (BCa). MATERIALS AND METHODS: We confirmed ELF3 expression pattern in BCa cell lines using western blot; and in different grades of tumors using Immunohistochemistry. Cell invasion assay was employed to demonstrate potential role of ELF3 in EMT. RESULTS AND CONCLUSION: ELF3 showed selective expression in low-grade cell lines and tumor tissues. Overexpression of ELF3 in mesenchymal cell line UMUC3 resulted in reduced invasion and decreased expression of mesenchymal markers. We observed association of low ELF3 expression with increased risk and overall poor survival using publicly available data. ELF3-modulated reversal of EMT might be a useful strategy in the treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells. Conflicts of Interest The authors declare no conflict of interest. References 1 Iyer A., Gupta K., Sharma S., Hari K., Lee Y.F., Ramalingam N., Yap Y.S., West J., Bhagat A.A., Subramani B.V. Integrative Analysis and Machine Learning based Characterization of Single Circulating Tumor Cells. [Extracted from the article]