Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells

Piyush B. Gupta, Christine M. Fillmore, Guozhi Jiang, Sagi D. Shapira, Kai Tao, Charlotte Kuperwasser, Eric S. Lander

Research output: Contribution to journalArticlepeer-review

1150 Scopus citations

Abstract

Cancer cells within individual tumors often exist in distinct phenotypic states that differ in functional attributes. While cancer cell populations typically display distinctive equilibria in the proportion of cells in various states, the mechanisms by which this occurs are poorly understood. Here, we study the dynamics of phenotypic proportions in human breast cancer cell lines. We show that subpopulations of cells purified for a given phenotypic state return towards equilibrium proportions over time. These observations can be explained by a Markov model in which cells transition stochastically between states. A prediction of this model is that, given certain conditions, any subpopulation of cells will return to equilibrium phenotypic proportions over time. A second prediction is that breast cancer stem-like cells arise de novo from non-stem-like cells. These findings contribute to our understanding of cancer heterogeneity and reveal how stochasticity in single-cell behaviors promotes phenotypic equilibrium in populations of cancer cells.

Original languageEnglish
Pages (from-to)633-644
Number of pages12
JournalCell
Volume146
Issue number4
DOIs
StatePublished - Aug 19 2011

Bibliographical note

Funding Information:
We thank Aviv Regev, Robert Weinberg, Todd Golub, and Gaorav Gupta for valuable discussions and criticism of the manuscript, Supriya Gupta for assistance with gene-expression profiling, and Tom DiCesare for assistance with graphical design. This work was supported by the Breast Cancer Research Foundation, the Raymond and Beverly Sackler Foundation, and the Broad Institute.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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