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

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    Copyright: Valdés-Mora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    Date Issued
    2017-04-18
    Publisher Version
    10.18632/oncotarget.15815
    Author(s)
    Valdés-Mora, Fatima
    Locke, Warwick J.
    Bandrés, Eva
    Gallego-Ortega, David
    Cejas, Paloma
    García-Cabezas, Miguel Angel
    Colino-Sanguino, Yolanda
    Feliú, Jaime
    Del Pulgar, Teresa Gómez
    Lacal, Juan Carlos
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    Permanent Link
    https://hdl.handle.net/2144/28911
    Citation (published version)
    Fatima Valdés-Mora, Warwick J Locke, Eva Bandrés, David Gallego-Ortega, Paloma Cejas, Miguel Angel García-Cabezas, Yolanda Colino-Sanguino, Jaime Feliú, Teresa Gómez Del Pulgar, Juan Carlos Lacal. 2017. "Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.." Oncotarget, Volume 8, Issue 16, pp. 26755 - 26770.
    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.
    Rights
    Copyright: Valdés-Mora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    • BU Open Access Articles [4757]
    • SAR: Health Sciences: Scholarly Papers [114]


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