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Biomolecules 2015, 5(4), 2854-2876; doi:10.3390/biom5042854

Novel Implications of DNA Damage Response in Drug Resistance of Malignant Cancers Obtained from the Functional Interaction between p53 Family and RUNX2

Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan
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Academic Editors: Wolf-Dietrich Heyer, Thomas Helleday and Fumio Hanaoka
Received: 2 June 2015 / Revised: 17 September 2015 / Accepted: 16 October 2015 / Published: 23 October 2015
(This article belongs to the Special Issue DNA Damage Response)
View Full-Text   |   Download PDF [609 KB, uploaded 23 October 2015]   |  

Abstract

During the lifespan of cells, their genomic DNA is continuously exposed to theendogenous and exogenous DNA insults. Thus, the appropriate cellular response to DNAdamage plays a pivotal role in maintaining genomic integrity and also acts as a molecularbarrier towards DNA legion-mediated carcinogenesis. The tumor suppressor p53 participatesin an integral part of proper regulation of DNA damage response (DDR). p53 is frequentlymutated in a variety of human cancers. Since mutant p53 displays a dominant-negative behavioragainst wild-type p53, cancers expressing mutant p53 sometimes acquire drug-resistantphenotype, suggesting that mutant p53 prohibits the p53-dependent cell death pathwayfollowing DNA damage, and thereby contributing to the acquisition and/or maintenance ofdrug resistance of malignant cancers. Intriguingly, we have recently found that silencing ofpro-oncogenic RUNX2 enhances drug sensitivity of aggressive cancer cells regardless of p53status. Meanwhile, cancer stem cells (CSCs) have stem cell properties such as drug resistance.Therefore, the precise understanding of the biology of CSCs is quite important to overcometheir drug resistance. In this review, we focus on molecular mechanisms behind DDR as wellas the serious drug resistance of malignant cancers and discuss some attractive approachesto improving the outcomes of patients bearing drug-resistant cancers. View Full-Text
Keywords: AKT; anti-cancer drug; cancer stem cell; CD133; cell cycle arrest; cell death; DNA damage; drug resistance; p53 family; RUNX family AKT; anti-cancer drug; cancer stem cell; CD133; cell cycle arrest; cell death; DNA damage; drug resistance; p53 family; RUNX family
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ozaki, T.; Nakamura, M.; Shimozato, O. Novel Implications of DNA Damage Response in Drug Resistance of Malignant Cancers Obtained from the Functional Interaction between p53 Family and RUNX2. Biomolecules 2015, 5, 2854-2876.

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