Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts.
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ICR Authors
Authors
Calvo, F
Ranftl, R
Hooper, S
Farrugia, AJ
Moeendarbary, E
Bruckbauer, A
Batista, F
Charras, G
Sahai, E
Ranftl, R
Hooper, S
Farrugia, AJ
Moeendarbary, E
Bruckbauer, A
Batista, F
Charras, G
Sahai, E
Document Type
Journal Article
Date
2015-12-29
Date Accepted
2015-11-16
Date Available
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.
Citation
Cell reports, 2015, 13 (12), pp. 2699 - 2714
Source Title
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Drug Target Discovery
Tumour Microenvironment
Tumour Microenvironment