Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts
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Calvo-2015-Cdc42EP3_BORG2 and S.pdf
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Author(s)
Calvo, Fernando
Ranftl, Romana
Hooper, Steven
Farrugia, Aaron J.
Moeendarbary, Emad
Bruckbauer, Andreas
Batista, Facundo
Charras, Guillaume
Sahai, Erik
Date Issued
December 2015
Journal
Cell Reports
Publisher
Elsevier
Citation
Calvo, Fernando, Romana Ranftl, Steven Hooper, Aaron J. Farrugia, Emad Moeendarbary, Andreas Bruckbauer, Facundo Batista, Guillaume Charras, and Erik Sahai. “Cdc42EP3/BORG2 and Septin Network Enables Mechano-Transduction and the Emergence of Cancer-Associated Fibroblasts.” Cell Reports 13, no. 12 (December 2015): 2699–2714.
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Final published version
Abstract
Cancer-associated fibroblasts (CAFs) are non-cancerous cells found in solid tumors that remodel the tumor matrix and promote cancer invasion and angiogenesis. Here, we demonstrate that Cdc42EP3/BORG2 is required for the matrix remodeling, invasion, angiogenesis, and tumor-growth-promoting abilities of CAFs. Cdc42EP3 functions by coordinating the actin and septin networks. Furthermore, depletion of SEPT2 has similar effects to those of loss of Cdc42EP3, indicating a role for the septin network in the tumor stroma. Cdc42EP3 is upregulated early in fibroblast activation and precedes the emergence of the highly contractile phenotype characteristic of CAFs. Depletion of Cdc42EP3 in normal fibroblasts prevents their activation by cancer cells. We propose that Cdc42EP3 sensitizes fibroblasts to further cues—in particular, those activating actomyosin contractility—and thereby enables the generation of the pathological activated fibroblast state.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2015.11.052
