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Int J Mol Sci. 2016 Nov 30;17(12). pii: E2003.

Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma.

Author information

1
Cancer Research Center-IBMCC (USAL-CSIC), 37007 Salamanca, Spain. anah@usal.es.
2
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain. anah@usal.es.
3
Cancer Research Center-IBMCC (USAL-CSIC), 37007 Salamanca, Spain. elirr@usal.es.
4
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain. elirr@usal.es.
5
Cancer Research Center-IBMCC (USAL-CSIC), 37007 Salamanca, Spain. irenamk@usal.es.
6
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain. irenamk@usal.es.
7
National Medicines Institute, 00725 Warsaw, Poland. irenamk@usal.es.
8
Cancer Research Center-IBMCC (USAL-CSIC), 37007 Salamanca, Spain. patrykk@usal.es.
9
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain. patrykk@usal.es.
10
Cancer Research Center-IBMCC (USAL-CSIC), 37007 Salamanca, Spain. normagu@usal.es.
11
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain. normagu@usal.es.
12
Hematology Department, University Hospital of Salamanca, 37007 Salamanca, Spain. normagu@usal.es.

Abstract

The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation. Translational implications for MM and cancer prognosis and treatment are also reviewed.

KEYWORDS:

TP53 methylation; TP53 mutations; TP53 splicing; cancer; epigenetics; miRNAs; myeloma; p53; p53-based therapy

PMID:
27916892
PMCID:
PMC5187803
DOI:
10.3390/ijms17122003
[Indexed for MEDLINE]
Free PMC Article

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