Please use this identifier to cite or link to this item:
Title: Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer
Author: Sanz Pamplona, Rebeca
Berenguer, Antoni
Cordero Romera, David
Garcia i Molleví, David
Crous Bou, Marta
Solé Acha, Xavier
Paré, Laia
Guinó, Elisabet
Salazar Soler, Ramón
Santos, Cristina
Oca Burguete, Javier de
Sanjuan, Xavier
Rodríguez Moranta, Francisco
Moreno Aguado, Víctor
Keywords: Càncer colorectal
Mucosa gastrointestinal
Colorectal cancer
Gastrointestinal mucosa
Issue Date: 5-Mar-2014
Publisher: BioMed Central
Abstract: Background: A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient's gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods: A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results: Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions: The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients
Note: Reproducció del document publicat a:
It is part of: Molecular Cancer, 2014, vol. 13, num. 46, p. 1-19
Related resource:
ISSN: 1476-4598
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
646665.pdf3.07 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons