An epigenetically distinct breast cancer cell subpopulation promotes collective invasion

Jill M. Westcott, Amanda M. Prechtl, Erin A. Maine, Tuyen T. Dang, Matthew A. Esparza, Han Sun, Yunyun Zhou, Yang Xie, Gray W. Pearson

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Tumor cells can engage in a process called collective invasion, in which cohesive groups of cells invade through interstitial tissue. Here, we identified an epigenetically distinct subpopulation of breast tumor cells that have an enhanced capacity to collectively invade. Analysis of spheroid invasion in an organotypic culture system revealed that these "trailblazer" cells are capable of initiating collective invasion and promote non-trailblazer cell invasion, indicating a commensal relationship among subpopulations within heterogenous tumors. Canonical mesenchymal markers were not sufficient to distinguish trailblazer cells from non-trailblazer cells, suggesting that defining the molecular underpinnings of the trailblazer phenotype could reveal collective invasion-specific mechanisms. Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B, and LPAR1 are highly expressed in trailblazer cells and required to initiate collective invasion, with DOCK10 essential for metastasis. In patients with triple-negative breast cancer, expression of these 7 genes correlated with poor outcome. Together, our results indicate that spontaneous conversion of the epigenetic state in a subpopulation of cells can promote a transition from in situ to invasive growth through induction of a cooperative form of collective invasion and suggest that therapeutic inhibition of trailblazer cell invasion may help prevent metastasis.

Original languageEnglish (US)
Pages (from-to)1927-1943
Number of pages17
JournalJournal of Clinical Investigation
Volume125
Issue number5
DOIs
StatePublished - May 1 2015

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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasm Metastasis
Epigenomics
Neoplasms
Phenotype
Gene Expression
Growth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

An epigenetically distinct breast cancer cell subpopulation promotes collective invasion. / Westcott, Jill M.; Prechtl, Amanda M.; Maine, Erin A.; Dang, Tuyen T.; Esparza, Matthew A.; Sun, Han; Zhou, Yunyun; Xie, Yang; Pearson, Gray W.

In: Journal of Clinical Investigation, Vol. 125, No. 5, 01.05.2015, p. 1927-1943.

Research output: Contribution to journalArticle

Westcott, JM, Prechtl, AM, Maine, EA, Dang, TT, Esparza, MA, Sun, H, Zhou, Y, Xie, Y & Pearson, GW 2015, 'An epigenetically distinct breast cancer cell subpopulation promotes collective invasion', Journal of Clinical Investigation, vol. 125, no. 5, pp. 1927-1943. https://doi.org/10.1172/JCI77767
Westcott JM, Prechtl AM, Maine EA, Dang TT, Esparza MA, Sun H et al. An epigenetically distinct breast cancer cell subpopulation promotes collective invasion. Journal of Clinical Investigation. 2015 May 1;125(5):1927-1943. https://doi.org/10.1172/JCI77767
Westcott, Jill M. ; Prechtl, Amanda M. ; Maine, Erin A. ; Dang, Tuyen T. ; Esparza, Matthew A. ; Sun, Han ; Zhou, Yunyun ; Xie, Yang ; Pearson, Gray W. / An epigenetically distinct breast cancer cell subpopulation promotes collective invasion. In: Journal of Clinical Investigation. 2015 ; Vol. 125, No. 5. pp. 1927-1943.
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