Mitochondrial dynamics in cancer stem cells

Abstract

Many tumors are now understood to be heterogenous cell populations arising from a minority of epithelial-like cancer stem cells (CSCs). CSCs demonstrate distinctive metabolic signatures from the more differentiated surrounding tumor bulk that confer resistance to traditional chemotherapeutic regimens and potential for tumor relapse. Many CSC phenotypes including metabolism, epithelial-to-mesenchymal transition, cellular signaling pathway activity, and others, arise from altered mitochondrial function and turnover, which are regulated by constant cycles of mitochondrial fusion and fission. Further, recycling of mitochondria through mitophagy in CSCs is associated with maintenance of reactive oxygen species levels that dictate gene expression. The protein machinery that drives mitochondrial dynamics is surprisingly simple and may represent attractive new therapeutic avenues to target CSC metabolism and selectively eradicate tumor-generating cells to reduce the risks of metastasis and relapse for a variety of tumor types.

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Acknowledgements

We thank the members of the Kashatus lab for review of the manuscript.

Funding

This work is supported by NIH grant CA200755 (to D.F.K.).

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Correspondence to David F. Kashatus.

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Sessions, D.T., Kashatus, D.F. Mitochondrial dynamics in cancer stem cells. Cell. Mol. Life Sci. (2021). https://doi.org/10.1007/s00018-021-03773-2

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Keywords

  • Mitochondrial dynamics
  • Mitochondrial morphology
  • Cancer stem cells
  • Metabolism
  • Therapeutic resistance
  • Signaling
  • EMT