File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk

TitleThe interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk
Authors
Keywordsintravital microscopy
cancer
Src
alpha5-integrin
Rho-GTPase
caveolin-1
Issue Date2012
Citation
Oncogene, 2012, v. 31, n. 7, p. 884-896 How to Cite?
AbstractProteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130 Cas, which is crucial for both normal cell migration and Src kinase-mediated metastasis of cancer cells. However, although Rho-GTPases (particularly RhoC) and Cav1 have been linked to cancer progression and metastasis, the underlying molecular mechanisms are largely unknown. To investigate the function of Cav1-Rho-GTPase interaction in metastasis, we disrupted Cav1-Rho-GTPase binding in melanoma and mammary epithelial tumor cells by overexpressing CBD, and examined the loss-of-function of RhoC in metastatic cancer cells. Cancer cells overexpressing CBD or lacking RhoC had reduced p130 Cas phosphorylation and Rac1 activation, resulting in an inhibition of migration and invasion in vitro. The activity of Src and the activation of its downstream targets FAK, Pyk2, Ras and extracellular signal-regulated kinase (Erk)1/2 were also impaired. A reduction in α5-integrin expression, which is required for binding to fibronectin and thus cell migration and survival, was observed in CBD-expressing cells and cells lacking RhoC. As a result of these defects, CBD-expressing melanoma cells had a reduced ability to metastasize in recipient mice, and impaired extravasation and survival in secondary sites in chicken embryos. Our data indicate that interaction between Cav1 and Rho-GTPases (most likely RhoC but not RhoA) promotes metastasis by stimulating α5-integrin expression and regulating the Src-dependent activation of p130 Cas/Rac1, FAK/Pyk2 and Ras/Erk1/2 signaling cascades.
Persistent Identifierhttp://hdl.handle.net/10722/292688
ISSN
2023 Impact Factor: 6.9
2023 SCImago Journal Rankings: 2.334
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorArpaia, E.-
dc.contributor.authorBlaser, H.-
dc.contributor.authorQuintela-Fandino, M.-
dc.contributor.authorDuncan, G.-
dc.contributor.authorLeong, H. S.-
dc.contributor.authorAblack, A.-
dc.contributor.authorNambiar, S. C.-
dc.contributor.authorLind, E. F.-
dc.contributor.authorSilvester, J.-
dc.contributor.authorFleming, C. K.-
dc.contributor.authorRufini, A.-
dc.contributor.authorTusche, M. W.-
dc.contributor.authorBrüstle, A.-
dc.contributor.authorOhashi, P. S.-
dc.contributor.authorLewis, J. D.-
dc.contributor.authorMak, T. W.-
dc.date.accessioned2020-11-17T14:57:00Z-
dc.date.available2020-11-17T14:57:00Z-
dc.date.issued2012-
dc.identifier.citationOncogene, 2012, v. 31, n. 7, p. 884-896-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10722/292688-
dc.description.abstractProteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130 Cas, which is crucial for both normal cell migration and Src kinase-mediated metastasis of cancer cells. However, although Rho-GTPases (particularly RhoC) and Cav1 have been linked to cancer progression and metastasis, the underlying molecular mechanisms are largely unknown. To investigate the function of Cav1-Rho-GTPase interaction in metastasis, we disrupted Cav1-Rho-GTPase binding in melanoma and mammary epithelial tumor cells by overexpressing CBD, and examined the loss-of-function of RhoC in metastatic cancer cells. Cancer cells overexpressing CBD or lacking RhoC had reduced p130 Cas phosphorylation and Rac1 activation, resulting in an inhibition of migration and invasion in vitro. The activity of Src and the activation of its downstream targets FAK, Pyk2, Ras and extracellular signal-regulated kinase (Erk)1/2 were also impaired. A reduction in α5-integrin expression, which is required for binding to fibronectin and thus cell migration and survival, was observed in CBD-expressing cells and cells lacking RhoC. As a result of these defects, CBD-expressing melanoma cells had a reduced ability to metastasize in recipient mice, and impaired extravasation and survival in secondary sites in chicken embryos. Our data indicate that interaction between Cav1 and Rho-GTPases (most likely RhoC but not RhoA) promotes metastasis by stimulating α5-integrin expression and regulating the Src-dependent activation of p130 Cas/Rac1, FAK/Pyk2 and Ras/Erk1/2 signaling cascades.-
dc.languageeng-
dc.relation.ispartofOncogene-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectintravital microscopy-
dc.subjectcancer-
dc.subjectSrc-
dc.subjectalpha5-integrin-
dc.subjectRho-GTPase-
dc.subjectcaveolin-1-
dc.titleThe interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/onc.2011.288-
dc.identifier.pmid21765460-
dc.identifier.pmcidPMC3289793-
dc.identifier.scopuseid_2-s2.0-84857118750-
dc.identifier.volume31-
dc.identifier.issue7-
dc.identifier.spage884-
dc.identifier.epage896-
dc.identifier.eissn1476-5594-
dc.identifier.isiWOS:000300615800007-
dc.identifier.issnl0950-9232-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats