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Cdc42 promotes transendothelial migration of cancer cells through β1 integrin

Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell–endothelial cell interactions and transendothelial migration. We find th...

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Autores principales: Reymond, Nicolas, Im, Jae Hong, Garg, Ritu, Vega, Francisco M., Borda d’Agua, Barbara, Riou, Philippe, Cox, Susan, Valderrama, Ferran, Muschel, Ruth J., Ridley, Anne J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494849/
https://www.ncbi.nlm.nih.gov/pubmed/23148235
http://dx.doi.org/10.1083/jcb.201205169
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author Reymond, Nicolas
Im, Jae Hong
Garg, Ritu
Vega, Francisco M.
Borda d’Agua, Barbara
Riou, Philippe
Cox, Susan
Valderrama, Ferran
Muschel, Ruth J.
Ridley, Anne J.
author_facet Reymond, Nicolas
Im, Jae Hong
Garg, Ritu
Vega, Francisco M.
Borda d’Agua, Barbara
Riou, Philippe
Cox, Susan
Valderrama, Ferran
Muschel, Ruth J.
Ridley, Anne J.
author_sort Reymond, Nicolas
collection PubMed
description Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell–endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates β1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). β1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous β1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying β1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function.
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spelling pubmed-34948492013-05-12 Cdc42 promotes transendothelial migration of cancer cells through β1 integrin Reymond, Nicolas Im, Jae Hong Garg, Ritu Vega, Francisco M. Borda d’Agua, Barbara Riou, Philippe Cox, Susan Valderrama, Ferran Muschel, Ruth J. Ridley, Anne J. J Cell Biol Research Articles Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell–endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates β1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). β1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous β1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying β1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function. The Rockefeller University Press 2012-11-12 /pmc/articles/PMC3494849/ /pubmed/23148235 http://dx.doi.org/10.1083/jcb.201205169 Text en © 2012 Reymond et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Reymond, Nicolas
Im, Jae Hong
Garg, Ritu
Vega, Francisco M.
Borda d’Agua, Barbara
Riou, Philippe
Cox, Susan
Valderrama, Ferran
Muschel, Ruth J.
Ridley, Anne J.
Cdc42 promotes transendothelial migration of cancer cells through β1 integrin
title Cdc42 promotes transendothelial migration of cancer cells through β1 integrin
title_full Cdc42 promotes transendothelial migration of cancer cells through β1 integrin
title_fullStr Cdc42 promotes transendothelial migration of cancer cells through β1 integrin
title_full_unstemmed Cdc42 promotes transendothelial migration of cancer cells through β1 integrin
title_short Cdc42 promotes transendothelial migration of cancer cells through β1 integrin
title_sort cdc42 promotes transendothelial migration of cancer cells through β1 integrin
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494849/
https://www.ncbi.nlm.nih.gov/pubmed/23148235
http://dx.doi.org/10.1083/jcb.201205169
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