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p53-Dependent and -Independent Epithelial Integrity: Beyond miRNAs and Metabolic Fluctuations

Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan
Author to whom correspondence should be addressed.
Cancers 2018, 10(6), 162;
Received: 3 April 2018 / Revised: 22 May 2018 / Accepted: 23 May 2018 / Published: 25 May 2018
(This article belongs to the Special Issue p53 Signaling in Cancers)
In addition to its classical roles as a tumor suppressor, p53 has also been shown to act as a guardian of epithelial integrity by inducing the microRNAs that target transcriptional factors driving epithelial–mesenchymal transition. On the other hand, the ENCODE project demonstrated an enrichment of putative motifs for the binding of p53 in epithelial-specific enhancers, such as CDH1 (encoding E-cadherin) enhancers although its biological significance remained unknown. Recently, we identified two novel modes of epithelial integrity (i.e., maintenance of CDH1 expression): one involves the binding of p53 to a CDH1 enhancer region and the other does not. In the former, the binding of p53 is necessary to maintain permissive histone modifications around the CDH1 transcription start site, whereas in the latter, p53 does not bind to this region nor affect histone modifications. Furthermore, these mechanisms likely coexisted within the same tissue. Thus, the mechanisms involved in epithelial integrity appear to be much more complex than previously thought. In this review, we describe our findings, which may instigate further experimental scrutiny towards understanding the whole picture of epithelial integrity as well as the related complex asymmetrical functions of p53. Such understanding will be important not only for cancer biology but also for the safety of regenerative medicine. View Full-Text
Keywords: p53; EMT; epithelial integrity; histone modification; miRNAs p53; EMT; epithelial integrity; histone modification; miRNAs
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Oikawa, T.; Otsuka, Y.; Sabe, H. p53-Dependent and -Independent Epithelial Integrity: Beyond miRNAs and Metabolic Fluctuations. Cancers 2018, 10, 162.

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