Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells
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,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92332 https://orcid.org/0000-0002-9703-1780 |
| _version_ | 1826213241147097088 |
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| author | Fillmore, Christine M. Jiang, Guozhi Shapira, Sagi D. Tao, Kai Kuperwasser, Charlotte Gupta, Piyush Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Fillmore, Christine M. Jiang, Guozhi Shapira, Sagi D. Tao, Kai Kuperwasser, Charlotte Gupta, Piyush Lander, Eric Steven |
| author_sort | Fillmore, Christine M. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:45:41Z |
| format | Article |
| id | mit-1721.1/92332 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:45:41Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/923322022-09-29T15:58:36Z Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells Fillmore, Christine M. Jiang, Guozhi Shapira, Sagi D. Tao, Kai Kuperwasser, Charlotte Gupta, Piyush Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric S. Gupta, Piyush 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. Broad Institute of MIT and Harvard Breast Cancer Research Foundation Raymond and Beverley Sackler Foundation 2014-12-16T17:53:51Z 2014-12-16T17:53:51Z 2011-08 2011-03 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/92332 Gupta, Piyush B., Christine M. Fillmore, Guozhi Jiang, Sagi D. Shapira, Kai Tao, Charlotte Kuperwasser, and Eric S. Lander. “Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells.” Cell 146, no. 4 (August 2011): 633–644. © 2011 Elsevier Inc. https://orcid.org/0000-0002-9703-1780 en_US http://dx.doi.org/10.1016/j.cell.2011.07.026 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Fillmore, Christine M. Jiang, Guozhi Shapira, Sagi D. Tao, Kai Kuperwasser, Charlotte Gupta, Piyush Lander, Eric Steven Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells |
| title | Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells |
| title_full | Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells |
| title_fullStr | Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells |
| title_full_unstemmed | Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells |
| title_short | Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells |
| title_sort | stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells |
| url | http://hdl.handle.net/1721.1/92332 https://orcid.org/0000-0002-9703-1780 |
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