Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000689020300001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3390/cancers13164072
eISSN
2072-6694
Externe Identifier
  • Clarivate Analytics Document Solution ID: UG1KN
  • PubMed Identifier: 34439227
Ausgabe der Veröffentlichung
16
Zeitschrift
CANCERS
Schlüsselwörter
  • acetylation
  • carcinogenesis
  • methylation
  • micro-RNA
  • oncogene
  • signal transduction
  • tumor suppressor
Artikelnummer
ARTN 4072
Datum der Veröffentlichung
2021
Status
Published
Titel
Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma
Sub types
  • Review
Ausgabe der Zeitschrift
13

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>Colorectal cancer (CRC) belongs to the most common tumor types, and half of all CRC harbor missense mutations in the TP53 tumor suppressor gene. In addition to genetically caused loss of function of p53, epigenetic alterations (DNA methylation, histone modifications, micro-RNAs) contribute to CRC development. In this review, we focused on epigenetic alterations related to the entire p53 signaling pathway upstream and downstream of p53. Methylation of genes which activate p53 function has been reported, and methylation of APC and MGMT was associated with increased mutation rates of TP53. The micro-RNA 34a activates TP53 and was methylated in CRC. Proteins that regulate TP53 DNA methylation, mutations, and acetylation of TP53-related histones were methylated in CRC. P53 regulates the activity of numerous downstream proteins. Even if TP53 is not mutated, the function of wildtype p53 may be compromised if corresponding downstream genes are epigenetically inactivated. Thus, the role of p53 for CRC development, therapy response, and survival prognosis of patients may be much more eminent than previously estimated. Therefore, we propose that novel diagnostic devices measuring the entirety of genetic and epigenetic changes in the “p53 signalome” have the potential to improve the predictive and prognostic power in CRC diagnostics and management.</jats:p>
Autoren
DOI
10.3390/cancers13164072
eISSN
2072-6694
Ausgabe der Veröffentlichung
16
Zeitschrift
Cancers
Sprache
en
Online publication date
2021
Paginierung
4072 - 4072
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/cancers13164072
Datum der Datenerfassung
2021
Titel
Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma
Ausgabe der Zeitschrift
13

Data source: Crossref

Abstract
Colorectal cancer (CRC) belongs to the most common tumor types, and half of all CRC harbor missense mutations in the <i>TP53</i> tumor suppressor gene. In addition to genetically caused loss of function of p53, epigenetic alterations (DNA methylation, histone modifications, micro-RNAs) contribute to CRC development. In this review, we focused on epigenetic alterations related to the entire p53 signaling pathway upstream and downstream of p53. Methylation of genes which activate p53 function has been reported, and methylation of <i>APC</i> and <i>MGMT</i> was associated with increased mutation rates of <i>TP53</i>. The micro-RNA 34a activates <i>TP53</i> and was methylated in CRC. Proteins that regulate TP53 DNA methylation, mutations, and acetylation of TP53-related histones were methylated in CRC. P53 regulates the activity of numerous downstream proteins. Even if <i>TP53</i> is not mutated, the function of wildtype p53 may be compromised if corresponding downstream genes are epigenetically inactivated. Thus, the role of p53 for CRC development, therapy response, and survival prognosis of patients may be much more eminent than previously estimated. Therefore, we propose that novel diagnostic devices measuring the entirety of genetic and epigenetic changes in the "p53 signalome" have the potential to improve the predictive and prognostic power in CRC diagnostics and management.
Addresses
  • Department of Toxicology, University Medical Center, 55131 Mainz, Germany.
Autoren
DOI
10.3390/cancers13164072
eISSN
2072-6694
Externe Identifier
  • PubMed Identifier: 34439227
  • PubMed Central ID: PMC8394868
Open access
true
ISSN
2072-6694
Ausgabe der Veröffentlichung
16
Zeitschrift
Cancers
Sprache
eng
Medium
Electronic
Online publication date
2021
Open access status
Open Access
Paginierung
4072
Datum der Veröffentlichung
2021
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2021
Titel
Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma.
Sub types
  • review-article
  • Review
  • Journal Article
Ausgabe der Zeitschrift
13

Files

https://www.mdpi.com/2072-6694/13/16/4072/pdf?version=1629677600 https://europepmc.org/articles/PMC8394868?pdf=render

Data source: Europe PubMed Central

Abstract
Colorectal cancer (CRC) belongs to the most common tumor types, and half of all CRC harbor missense mutations in the TP53 tumor suppressor gene. In addition to genetically caused loss of function of p53, epigenetic alterations (DNA methylation, histone modifications, micro-RNAs) contribute to CRC development. In this review, we focused on epigenetic alterations related to the entire p53 signaling pathway upstream and downstream of p53. Methylation of genes which activate p53 function has been reported, and methylation of APC and MGMT was associated with increased mutation rates of TP53. The micro-RNA 34a activates TP53 and was methylated in CRC. Proteins that regulate TP53 DNA methylation, mutations, and acetylation of TP53-related histones were methylated in CRC. P53 regulates the activity of numerous downstream proteins. Even if TP53 is not mutated, the function of wildtype p53 may be compromised if corresponding downstream genes are epigenetically inactivated. Thus, the role of p53 for CRC development, therapy response, and survival prognosis of patients may be much more eminent than previously estimated. Therefore, we propose that novel diagnostic devices measuring the entirety of genetic and epigenetic changes in the "p53 signalome" have the potential to improve the predictive and prognostic power in CRC diagnostics and management.
Date of acceptance
2021
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/34439227
DOI
10.3390/cancers13164072
Externe Identifier
  • PubMed Central ID: PMC8394868
ISSN
2072-6694
Ausgabe der Veröffentlichung
16
Zeitschrift
Cancers (Basel)
Schlüsselwörter
  • acetylation
  • carcinogenesis
  • methylation
  • micro-RNA
  • oncogene
  • signal transduction
  • tumor suppressor
Sprache
eng
Country
Switzerland
PII
cancers13164072
Datum der Veröffentlichung
2021
Status
Published online
Titel
Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma.
Sub types
  • Journal Article
  • Review
Ausgabe der Zeitschrift
13

Data source: PubMed

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