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Biophysical and Epigenetic Regulation of Cancer Stemness, Invasiveness, and Immune Action

  • Cell Behavior Manipulation (S Willerth, Section Editor)
  • Published:
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Abstract

Purpose of Review

The tumor microenvironment (TME) is an amalgam of multiple dysregulated biophysical cues that can alter cellular behavior through mechanotransductive signaling and epigenetic modifications. Through this review, we seek to characterize the extent of biophysical and epigenetic regulation of cancer stemness and tumor-associated immune cells in order to identify ideal targets for cancer therapy.

Recent Findings

Recent studies have identified cancer stemness and immune action as significant contributors to neoplastic disease, due to their susceptibility to microenvironmental influences. Matrix stiffening, altered vasculature, and resultant hypoxia within the TME can influence cancer stem cell (CSC) and immune cell behavior, as well as alter the epigenetic landscapes involved in cancer development.

Summary

This review highlights the importance of aberrant biophysical cues in driving cancer progression through altered behavior of CSCs and immune cells, which in turn sustains further biophysical dysregulation. We examine current and potential therapeutic approaches that break this self-sustaining cycle of disease progression by targeting the presented biophysical and epigenetic signatures of cancer. We also summarize strategies including the normalization of the TME, targeted drug delivery, and inhibition of cancer-enabling epigenetic players.

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Acknowledgments

This work was supported by the National Institutes of Health (NIH) National Institute of Allergy and Infectious Disease (NIAID) Grant R21AI128519-01 to W.F.L, NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant R21EB027840-01 to T.L.D and W.F.L, and NIH New Innovator Award (DP2) Grant DP2CA250382-01, a National Science Foundation (NSF) grant (DMS1763272) and a grant from the Simons Foundation (594598 QN) to T.L.D. N.A. was supported by a T32 training grant from the NIH (T32HL116270).

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  1. Department of Biomedical Engineering, University of California-Irvine, Irvine, CA, USA

    Praveen Krishna Veerasubramanian, Navied Akhtar, Wendy F. Liu & Timothy L. Downing

  2. The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine, Irvine, CA, USA

    Praveen Krishna Veerasubramanian, Annie Trinh, Navied Akhtar, Wendy F. Liu & Timothy L. Downing

  3. Department of Microbiology and Molecular Genetics, University of California-Irvine, Irvine, CA, USA

    Annie Trinh & Timothy L. Downing

  4. Department of Chemical and Biomolecular Engineering, University of California-Irvine, Irvine, CA, USA

    Wendy F. Liu

  5. NSF-Simons Center for Multiscale Cell Fate Research, University of California-Irvine, Irvine, CA, USA

    Timothy L. Downing

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Veerasubramanian, P.K., Trinh, A., Akhtar, N. et al. Biophysical and Epigenetic Regulation of Cancer Stemness, Invasiveness, and Immune Action. Curr. Tissue Microenviron. Rep. 1, 277–300 (2020). https://doi.org/10.1007/s43152-020-00021-w

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