Epigenetic regulation of cancer-associated fibroblast heterogeneity

Rachel J. Kehrberg, Namita Bhyravbhatla, Surinder K. Batra, Sushil Kumar

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Cancer-associated fibroblasts (CAFs), a significant component of the tumor microenvironment (TME), contribute to cancer progression through the secretion of extracellular matrix (ECM), growth factors, and metabolites. It is now well recognized that CAFs are a heterogenous population with ablation experiments leading to reduced tumor growth and single-cell RNA sequencing demonstrating CAF subgroups. CAFs lack genetic mutations yet substantially differ from their normal stromal precursors. Here, we review epigenetic changes in CAF maturation, focusing on DNA methylation and histone modifications. DNA methylation changes in CAFs have been demonstrated globally, while roles of methylation at specific genes affect tumor growth. Further, loss of CAF histone methylation and gain of histone acetylation has been shown to promote CAF activation and tumor promotion. Many CAF activating factors, such as transforming growth factor β (TGFβ), lead to these epigenetic changes. MicroRNAs (miRNAs) serve as targets and orchestrators of epigenetic modifications that influence gene expression. Bromodomain and extra-terminal domain (BET), an epigenetic reader, recognizes histone acetylation and activates the transcription of genes leading to the pro-tumor phenotype of CAFs.

Original languageEnglish (US)
Article number188901
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1878
Issue number3
DOIs
StatePublished - May 2023

Keywords

  • Cancer-associated fibroblasts
  • DNA methylation
  • Epigenetics
  • Histone acetylation
  • Histone methylation
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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