Investigation of the role of tyrosine kinase receptor EPHA3 in colorectal cancer
Andretta, Elena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Cartón-Garcia, Fernando (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez-Barriocanal, Águeda (Hospital Universitari Vall d'Hebron. Institut de Recerca)
de Marcondes, Priscila Guimarães (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Jimenez-Flores, Lizbeth M. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Macaya, Irati (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bazzocco, Sarah (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bilic Zimmermann, Josipa (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodrigues, Paulo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nieto Raya, Rocio (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Landolfi, Stefania (Hospital Universitari Vall d'Hebron)
Ramon y Cajal, Santiago (Hospital Universitari Vall d'Hebron)
Schwartz, Simo (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Brown, Arthur (Robarts Research Institute)
Dopeso, Higinio (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Arango, Diego (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	EPH signaling deregulation has been shown to be important for colorectal carcinogenesis and genome-wide sequencing efforts have identified EPHA3 as one of the most frequently mutated genes in these tumors. However, the role of EPHA3 in colorectal cancer has not been thoroughly investigated. We show here that ectopic expression of wild type EPHA3 in colon cancer cells did not affect their growth, motility/invasion or metastatic potential in vivo. Moreover, overexpression of mutant EPHA3 or deletion of the endogenous mutant EPHA3 in colon cancer cells did not affect their growth or motility. EPHA3 inactivation in mice did not initiate the tumorigenic process in their intestine, and had no effects on tumor size/multiplicity after tumor initiation either genetically or pharmacologically. In addition, immunohistochemical analysis of EPHA3 tumor levels did not reveal associations with survival or clinicopathological features of colorectal cancer patients. In conclusion, we show that EPHA3 does not play a major role in colorectal tumorigenesis. These results significantly contribute to our understanding of the role of EPH signaling during colorectal carcinogenesis, and highlighting the need for detailed functional studies to confirm the relevance of putative cancer driver genes identified in sequencing efforts of the cancer genome.
Grants:	Ministerio de Sanidad y Consumo CP05/00256 Ministerio de Ciencia e Innovación TRA2009-0093 Ministerio de Ciencia e Innovación SAF2008-00789 Ministerio de Ciencia e Innovación PI12/03103 Ministerio de Ciencia e Innovación PI12/01095 Ministerio de Ciencia e Innovación PI16/00540 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR 157
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan aquestes es distribueixin sota la mateixa llicència que regula l'obra original i es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 7 (02 2017) , ISSN 2045-2322

DOI: 10.1038/srep41576
PMID: 28169277

14 p, 2.1 MB

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