Significance of Epigenetic Alteration in Cancer-Associated Fibroblasts on the Development of Carcinoma

TL;DR

This review explores how epigenetic changes in cancer-associated fibroblasts influence tumor development and progression.

Contribution

The paper highlights the role of DNA methylation, histone acetylation, and enhancer reprogramming in CAFs as potential therapeutic targets.

Findings

Epigenetic alterations in CAFs are linked to transcriptional changes and patient outcomes in various tumors.

DNA methylation in CAFs can alter their state and influence tumor progression through multiple pathways.

Noncoding RNAs modulate CAF formation and therapeutic responses via interactions with tumor cells.

Abstract

Cancer-associated fibroblasts (CAFs) are a key constituent of the tumor microenvironment. CAFs may affect the development of tumor cells. The critical role of CAFs in the tumor microenvironment is linked to their epigenetic modifications, as a stable yet reversible regulation of cellular phenotypes. Current evidence indicates that their formation and function are closely linked to epigenetic mechanisms. Existing research indicates that the epigenetic alteration abnormalities are triggered by metabolic cues and stabilize the acquired phenotype of CAFs. This process is associated with transcriptional changes and patient outcomes in various tumors, providing a biological rationale and translational potential for reprogramming CAFs. Understanding of epigenetic modifications in CAFs remain insufficient, while DNA methylation in CAFs can alter CAF states through multiple pathways and thereby influence tumor progression. It is necessary to investigate the unique, identifiable epigenetic signatures of CAF. As an epigenetic reader couple histone acetylation to high-output oncogenic transcription; meanwhile, noncoding RNAs modulate CAF formation and therapeutic responses via bidirectional crosstalk between tumor cells and stroma. The interactions between different epigenetic modifications and their underlying regulatory logic may play a crucial role in developing new therapeutic strategies. This review focuses on the roles of DNA methylation, histone acetylation, and enhancer reprogramming in CAFs.

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