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Bridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization

Cell Death & Differentiation (2024)Cite this article

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Abstract

The epigenome coordinates spatial-temporal specific gene expression during development and in adulthood, for the maintenance of homeostasis and upon tissue repair. The upheaval of the epigenetic landscape is a key event in the onset of many pathologies including tumours, where epigenetic changes cooperate with genetic aberrations to establish the neoplastic phenotype and to drive cell plasticity during its evolution. DNA methylation, histone modifiers and readers or other chromatin components are indeed often altered in cancers, such as carcinomas that develop in epithelia. Lining the surfaces and the cavities of our body and acting as a barrier from the environment, epithelia are frequently subjected to acute or chronic tissue damages, such as mechanical injuries or inflammatory episodes. These events can activate plasticity mechanisms, with a deep impact on cells’ epigenome. Despite being very effective, tissue repair mechanisms are closely associated with tumour onset. Here we review the similarities between tissue repair and carcinogenesis, with a special focus on the epigenetic mechanisms activated by cells during repair and opted by carcinoma cells in multiple epithelia. Moreover, we discuss the recent findings on inflammatory and wound memory in epithelia and describe the epigenetic modifications that characterise them. Finally, as wound memory in epithelial cells promotes carcinogenesis, we highlight how it represents an early step for the establishment of field cancerization.

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Fig. 1: Tissue repair and carcinomas share multiple cellular phenotypes and epigenetic mechanisms.
Fig. 2: Epigenetic mechanisms of wound and inflammatory memories.
Fig. 3: Wound memory represents an early epigenetic field cancerization.

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Acknowledgements

Apologies to authors whose work could not be included due to space constraints. The Donati laboratory is supported by the Chan Zuckerberg Initiative (Single-Cell Analysis of Inflammation, Id. DAF2020-217532, https://doi.org/10.37921/173068fmftmj) and by AIRC, Associazione Italiana per la Ricerca sul Cancro (MFAG 2018 - Id. 21640).

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  1. These authors contributed equally: Chiara Levra Levron, Luca Elettrico.

Authors and Affiliations

  1. Department of Life Sciences and Systems Biology, University of Turin, Torino, Italy

    Chiara Levra Levron, Luca Elettrico, Carlotta Duval, Gabriele Piacenti, Valentina Proserpio & Giacomo Donati

  2. Molecular Biotechnology Center “Guido Tarone”, University of Turin, Torino, Italy

    Chiara Levra Levron, Luca Elettrico, Carlotta Duval, Gabriele Piacenti, Valentina Proserpio & Giacomo Donati

  3. Italian Institute for Genomic Medicine, Candiolo (TO), Italy

    Valentina Proserpio

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CLL and GD conceptualized the idea of the review. CLL, LE, and GD prepared the initial drafts of the manuscript. CD, GP, and VP contributed to the writing and manuscript improvement. CLL, LE, and GD contributed to the creation of figures and tables. All authors reviewed the manuscript and approved to the final version of this manuscript.

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Levra Levron, C., Elettrico, L., Duval, C. et al. Bridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization. Cell Death Differ (2024). https://doi.org/10.1038/s41418-023-01254-6

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