Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast

Christina Scheel, Elinor Ng Eaton, Sophia Hsin Jung Li, Christine L. Chaffer, Ferenc Reinhardt, Kong Jie Kah, George Bell, Wenjun Guo, Jeffrey Rubin, Andrea L. Richardson, Robert A. Weinberg

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558 Scopus citations

Abstract

The epithelial-mesenchymal transition (EMT) has been associated with the acquisition of motility, invasiveness, and self-renewal traits. During both normal development and tumor pathogenesis, this change in cell phenotype is induced by contextual signals that epithelial cells receive from their microenvironment. The signals that are responsible for inducing an EMT and maintaining the resulting cellular state have been unclear. We describe three signaling pathways, involving transforming growth factor (TGF)-β canonical and noncanonical Wnt signaling, that collaborate to induce activation of the EMT program and thereafter function in an autocrine fashion to maintain the resulting mesenchymal state. Downregulation of endogenously synthesized inhibitors of autocrine signals in epithelial cells enables the induction of the EMT program. Conversely, disruption of autocrine signaling by added inhibitors of these pathways inhibits migration and self-renewal in primary mammary epithelial cells and reduces tumorigenicity and metastasis by their transformed derivatives.

Original languageEnglish (US)
Pages (from-to)926-940
Number of pages15
JournalCell
Volume145
Issue number6
DOIs
StatePublished - Jun 10 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Scheel, C., Eaton, E. N., Li, S. H. J., Chaffer, C. L., Reinhardt, F., Kah, K. J., Bell, G., Guo, W., Rubin, J., Richardson, A. L., & Weinberg, R. A. (2011). Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell, 145(6), 926-940. https://doi.org/10.1016/j.cell.2011.04.029