Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma

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Updated: Oct 22, 2025

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Maja T Tomicic1, Mona Dawood2, Thomas Efferth2

  • 1Department of Toxicology, University Medical Center, 55131 Mainz, Germany.

Cancers
|August 27, 2021
PubMed

Insights

Epigenetic changes in colorectal cancer (CRC) impact the p53 signaling pathway, affecting tumor suppressor gene function. Targeting the "p53 signalome" could enhance CRC diagnostics and patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Colorectal cancer (CRC) is a common malignancy, frequently associated with TP53 mutations.
  • Epigenetic alterations, including DNA methylation and micro-RNA dysregulation, also contribute to CRC pathogenesis.
  • The p53 signaling pathway plays a critical role in cancer development and progression.

Purpose of the Study:

  • To review epigenetic alterations within the p53 signaling pathway in CRC.
  • To explore the impact of these alterations on p53 function and CRC development.
  • To propose novel diagnostic strategies based on the "p53 signalome".

Main Methods:

  • Literature review focusing on epigenetic modifications (DNA methylation, histone modifications, micro-RNAs) affecting the p53 pathway.
  • Analysis of studies linking epigenetic changes to TP53 mutations and p53 pathway activity.
  • Synthesis of evidence regarding the role of the p53 pathway in CRC.

Main Results:

  • Methylation of genes activating p53, such as APC and MGMT, correlates with increased TP53 mutation rates.
  • Micro-RNA 34a, an activator of TP53, is frequently methylated in CRC.
  • Epigenetic inactivation of p53 downstream targets can compromise wildtype p53 function.

Conclusions:

  • Epigenetic alterations significantly impact the p53 signaling pathway in CRC, beyond genetic mutations.
  • The p53 pathway's role in CRC development, therapy response, and prognosis may be underestimated.
  • Measuring the "p53 signalome" (genetic and epigenetic changes) offers potential for improved CRC diagnostics and management.
Keywords:
acetylationcarcinogenesismethylationmicro-RNAoncogenesignal transductiontumor suppressor

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