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CANCER MECHANOBIOLOGY

Epigenetic regulation of mechanotransduction

Nature Biomedical Engineering volume 5, pages 8–10 (2021)Cite this article

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The DNA methylation of the promoter region of the oncogenic Yes-associated protein is reversibly regulated by the stiffness of the extracellular matrix.

The extracellular matrix (ECM) of malignant tumours is often much stiffer than that of the healthy soft tissues from which the tumours originate. The mechanical contrast between malignant and healthy tissue can be so stark that manual palpation of a stiff lump in an otherwise soft tissue is frequently used in cancer screening. ECM stiffening (which results from increased ECM deposition and crosslinking, and from the structural remodelling of the existing fibre network1) has been seen in cancers of the breast, liver, pancreas, lung and brain, and in a number of other soft tissue cancers1. Enhanced ECM stiffness can exacerbate cancer-like traits, such as cell migration and invasion, and can promote malignant phenotypic transitions from non-malignant cells. Integrin binding, actomyosin contractility, mechanosignalling cascades, and transcription-factor activation and localization — often of the Yes-associated protein (YAP) — are all known to govern mechanotransduction of cells generally, and are also relevant in cancer. The role of epigenomic remodelling is however less known, notwithstanding epigenomic remodelling being broadly recognized as a major factor in the regulation of cell behaviours, and despite emerging evidence pointing at alterations in the cellular microenvironment inducing epigenomic changes2. Epigenomic remodelling involves chemical modifications to DNA (such as DNA methylation, which modulates gene expression and limits the interactions of DNA-binding proteins) and to histone proteins (which mediate DNA accessibility). Cancer epigenomes are often dysregulated, and epigenetic changes in cancer cells can confer all of the classical hallmarks of cancer3. Reporting in Nature Biomedical Engineering, Pilnam Kim, Jae-Ho Cheong, Jung Kyoon Choi and colleagues now show in a three-dimensional (3D) culture model of gastric cancer how matrix-stiffness-dependent DNA-methylation patterns on the YAP promoter itself mediate YAP activation and the induction of a malignant phenotype4.

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Fig. 1: Mechanisms of mechanotransduction and the role of the epigenome.

References

  1. Piersma, B., Hayward, M. K. & Weaver, V. M. Biochim. Biophys. Acta Rev. Cancer 1873, 188356 (2020).

    CAS  Article  Google Scholar 

  2. Nemec, S. & Kilian, K. A. Nat. Rev. Mater. https://doi.org/10.1038/s41578-020-00238-z (2020).

  3. Flavahan, W. A., Gaskell, E. & Bernstein, B. E. Science 357, eaal2380 (2017).

    Article  Google Scholar 

  4. Jang, M. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-020-00657-x (2020).

  5. Branco da Cunha, C. et al. Biomaterials 35, 8927–8936 (2014).

    CAS  Article  Google Scholar 

  6. Killaars, A. R. et al. Adv. Sci. 6, 1801483 (2019).

    Article  Google Scholar 

  7. Jain, N., Iyer, K. V., Kumar, A. & Shivashankar, G. V. Proc. Natl Acad. Sci. USA 110, 11349–11354 (2013).

    CAS  Article  Google Scholar 

  8. Stowers, R. S. et al. Nat. Biomed. Eng. 3, 1009–1019 (2019).

    Article  Google Scholar 

  9. Bintu, L. et al. Science 351, 720–724 (2016).

    CAS  Article  Google Scholar 

  10. Balestrini, J. L., Chaudhry, S., Sarrazy, V., Koehler, A. & Hinz, B. Integr. Biol. 4, 410–421 (2012).

    CAS  Article  Google Scholar 

  11. Yang, C., Tibbitt, M. W., Basta, L. & Anseth, K. S. Nat. Mater. 13, 645–652 (2014).

    CAS  Article  Google Scholar 

  12. Elosegui-Artola, A. et al. Nat. Cell Biol. 18, 540–548 (2016).

    CAS  Article  Google Scholar 

  13. Shiu, J.-Y., Aires, L., Lin, Z. & Vogel, V. Nat. Cell Biol. 20, 262–271 (2018).

    CAS  Article  Google Scholar 

  14. Lee, J. Y. et al. Nat. Commun. 10, 1848 (2019).

    Article  Google Scholar 

  15. Panciera, T. et al. Nat. Mater. 19, 797–806 (2020).

    CAS  Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Mechanical Engineering, Santa Barbara, CA, USA

    Ryan Stowers

  2. Center for Bioengineering, University of California, Santa Barbara, Santa Barbara, CA, USA

    Ryan Stowers

  3. Department of Mechanical Engineering, Stanford University, Stanford, CA, USA

    Ovijit Chaudhuri

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  1. Ryan Stowers
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  2. Ovijit Chaudhuri
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Correspondence to Ryan Stowers or Ovijit Chaudhuri.

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Stowers, R., Chaudhuri, O. Epigenetic regulation of mechanotransduction. Nat Biomed Eng 5, 8–10 (2021). https://doi.org/10.1038/s41551-020-00678-6

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