Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101697 https://orcid.org/0000-0002-7019-3907 |
| _version_ | 1826212748147556352 |
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| author | Calvo, Fernando Ranftl, Romana Hooper, Steven Farrugia, Aaron J. Moeendarbary, Emad Bruckbauer, Andreas Batista, Facundo Charras, Guillaume Sahai, Erik |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Calvo, Fernando Ranftl, Romana Hooper, Steven Farrugia, Aaron J. Moeendarbary, Emad Bruckbauer, Andreas Batista, Facundo Charras, Guillaume Sahai, Erik |
| author_sort | Calvo, Fernando |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:37:16Z |
| format | Article |
| id | mit-1721.1/101697 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:37:16Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1016972022-09-29T15:06:15Z Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts Calvo, Fernando Ranftl, Romana Hooper, Steven Farrugia, Aaron J. Moeendarbary, Emad Bruckbauer, Andreas Batista, Facundo Charras, Guillaume Sahai, Erik Massachusetts Institute of Technology. Department of Biological Engineering Moeendarbary, Emad 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. 2016-03-14T17:19:06Z 2016-03-14T17:19:06Z 2015-12 2015-09 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/101697 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. https://orcid.org/0000-0002-7019-3907 en_US http://dx.doi.org/10.1016/j.celrep.2015.11.052 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Calvo, Fernando Ranftl, Romana Hooper, Steven Farrugia, Aaron J. Moeendarbary, Emad Bruckbauer, Andreas Batista, Facundo Charras, Guillaume Sahai, Erik Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts |
| title | Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts |
| title_full | Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts |
| title_fullStr | Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts |
| title_full_unstemmed | Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts |
| title_short | Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts |
| title_sort | cdc42ep3 borg2 and septin network enables mechano transduction and the emergence of cancer associated fibroblasts |
| url | http://hdl.handle.net/1721.1/101697 https://orcid.org/0000-0002-7019-3907 |
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