Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.

Valdés-Mora, F; Locke, WJ; Bandrés, E; Gallego-Ortega, D; Cejas, P; García-Cabezas, MA; Colino-Sanguino, Y; Feliú, J; Del Pulgar, TG; Lacal, JC

Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.

Valdés-Mora, F Locke, WJ Bandrés, E Gallego-Ortega, D Cejas, P García-Cabezas, MA Colino-Sanguino, Y Feliú, J Del Pulgar, TG Lacal, JC

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Publisher:: IMPACT JOURNALS LLC
Publication Type:: Journal Article
Citation:: Oncotarget, 2017, 8, (16), pp. 26755-26770
Issue Date:: 2017-04-18

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Field	Value	Language
dc.contributor.author	Valdés-Mora, F
dc.contributor.author	Locke, WJ
dc.contributor.author	Bandrés, E
dc.contributor.author	Gallego-Ortega, D
dc.contributor.author	Cejas, P
dc.contributor.author	García-Cabezas, MA
dc.contributor.author	Colino-Sanguino, Y
dc.contributor.author	Feliú, J
dc.contributor.author	Del Pulgar, TG
dc.contributor.author	Lacal, JC
dc.date.accessioned	2022-04-13T12:28:08Z
dc.date.available	2017-02-20
dc.date.available	2022-04-13T12:28:08Z
dc.date.issued	2017-04-18
dc.identifier.citation	Oncotarget, 2017, 8, (16), pp. 26755-26770
dc.identifier.issn	1949-2553
dc.identifier.issn	1949-2553
dc.identifier.uri	http://hdl.handle.net/10453/156220
dc.description.abstract	CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC.
dc.format	Print
dc.language	eng
dc.publisher	IMPACT JOURNALS LLC
dc.relation.ispartof	Oncotarget
dc.relation.isbasedon	10.18632/oncotarget.15815
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.subject.mesh	Animals
dc.subject.mesh	Calcium Channels
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Movement
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Colorectal Neoplasms
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Gene Regulatory Networks
dc.subject.mesh	Genes, Tumor Suppressor
dc.subject.mesh	Heterografts
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Neoplasm Grading
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Neoplasm Staging
dc.subject.mesh	Prognosis
dc.subject.mesh	Reproducibility of Results
dc.subject.mesh	Transcriptome
dc.subject.mesh	cdc42 GTP-Binding Protein
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Colorectal Neoplasms
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	cdc42 GTP-Binding Protein
dc.subject.mesh	Calcium Channels
dc.subject.mesh	Neoplasm Staging
dc.subject.mesh	Prognosis
dc.subject.mesh	Reproducibility of Results
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Cell Movement
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Genes, Tumor Suppressor
dc.subject.mesh	Female
dc.subject.mesh	Gene Regulatory Networks
dc.subject.mesh	Neoplasm Grading
dc.subject.mesh	Transcriptome
dc.subject.mesh	Heterografts
dc.title	Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.
dc.type	Journal Article
utslib.citation.volume	8
utslib.location.activity	United States
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-13T12:28:01Z
pubs.issue	16
pubs.publication-status	Published
pubs.volume	8
utslib.citation.issue	16

Abstract:

CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC.

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http://hdl.handle.net/10453/156220