Cdc42EP3/BORG2 and septin network enables mechano-transduction and the emergence of cancer-associated fibroblasts
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2015-12-29
Date Acceptance
2015-11-16
Citation
Cell Reports, 2015, 13 (12), pp.2699-2714
ISSN
2211-1247
Publisher
Elsevier
Start Page
2699
End Page
2714
Journal / Book Title
Cell Reports
Volume
13
Issue
12
Copyright Statement
© 2015 The Author(s). This is an open access article under the CC BY-NC-ND license (
http://creativecommons.org/licenses/by-nc-nd/4.0/)
http://creativecommons.org/licenses/by-nc-nd/4.0/)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/26711338
PII: S2211-1247(15)01383-2
Subjects
Animals
Cell Line
Cell Line, Tumor
Fibroblasts
GTP-Binding Protein Regulators
Humans
Mice
Neoplasms
Septins
Up-Regulation
cdc42 GTP-Binding Protein
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2015-12-17