Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Journal Club
  • Published:

CANCER GENETICS

Stochastic transitions as a major source of cancer heterogeneity

Nature Reviews Genetics volume 23, pages 582–583 (2022)Cite this article

Subjects

Heterogeneity of cancer cells within a particular tumour (intra-tumour heterogeneity, ITH) has critical clinical significance, but the mechanisms that generate this heterogeneity are only partially understood and under constant debate. Arguably, the most widely appreciated mechanism is genetic — ongoing tumour evolution involves mutations and chromosomal aberrations that are restricted to subsets of cancer cells, thereby defining distinct genetic subclones. A second widely appreciated mechanism is the impact of the tumour microenvironment (TME), whereby cancer cells interact with other cells in their environment and are further influenced by hypoxia and various extracellular molecules.

Notably, a third mechanism is often neglected although it might be just as important as the other two. Cells undergo frequent stochastic transitions between distinct states, as elegantly demonstrated in 2011 by Gupta et al. in breast cancer cell lines, and subsequently shown for other cancer models. When cancer cells are sorted (for example, by surface markers) and a relatively pure population of cells in a particular state is followed over time, that population tends to regenerate the other states seen in the pre-sorted population within a few days, ultimately reverting back to the original frequencies of those states: the equilibrium or steady-state distribution.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

Original article

  • Gupta, P. B. et al. Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 146, 633–644 (2011)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

    Itay Tirosh

Authors
  1. Itay Tirosh
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Itay Tirosh.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tirosh, I. Stochastic transitions as a major source of cancer heterogeneity. Nat Rev Genet 23, 582–583 (2022). https://doi.org/10.1038/s41576-022-00508-2

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41576-022-00508-2

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer