Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast
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Scheel-2011-Paracrine and Autocr.pdf
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2.3 MB
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Author(s)
Scheel, Christina
Eaton, Elinor Ng
Chaffer, Christine L.
Reinhardt, Ferenc
Kah, Kong-Jie
Bell, George
Guo, Wenjun
Rubin, Jeffrey
Richardson, Andrea L.
Weinberg, Robert A.
Date Issued
June 2011
Journal
Cell
Publisher
Elsevier
Citation
Scheel, Christina, Elinor Ng Eaton, Sophia Hsin-Jung Li, Christine L. Chaffer, Ferenc Reinhardt, Kong-Jie Kah, George Bell, et al. “Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast.” Cell 145, no. 6 (June 2011): 926–940. © 2011 Elsevier Inc.
Version
Final published version
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 and 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
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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.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2011.04.029
