CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells

Stress has been proposed to be a tumor promoting factor through the secretion of specific neuromediators, such as Urocortin2 and 3 (Ucn2/3), however its role in colorectal cancer (CRC) remains elusive. We observed that Ucn2/3 and their receptor the Corticotropin Releasing Factor receptor 2 (CRF2) we...

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Main Authors: Ducarouge, Benjamin, Pelissier-Rota, Marjolaine, Lainé, Michèle, Cristina, Nadine, Vachez, Yvan, Scoazec, Jean-Yves, Bonaz, Bruno, Jacquier-Sarlin, Muriel
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832608/
id pubmed-3832608
recordtype oai_dc
spelling pubmed-38326082013-11-20 CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells Ducarouge, Benjamin Pelissier-Rota, Marjolaine Lainé, Michèle Cristina, Nadine Vachez, Yvan Scoazec, Jean-Yves Bonaz, Bruno Jacquier-Sarlin, Muriel Research Article Stress has been proposed to be a tumor promoting factor through the secretion of specific neuromediators, such as Urocortin2 and 3 (Ucn2/3), however its role in colorectal cancer (CRC) remains elusive. We observed that Ucn2/3 and their receptor the Corticotropin Releasing Factor receptor 2 (CRF2) were up-regulated in high grade and poorly differentiated CRC. This suggests a role for CRF2 in the loss of cellular organization and tumor progression. Using HT-29 and SW620 cells, two CRC cell lines differing in their abilities to perform cell-cell contacts, we found that CRF2 signals through Src/ERK pathway to induce the alteration of cell-cell junctions and the shuttle of p120ctn and Kaiso in the nucleus. In HT-29 cells, this signaling pathway also leads to the remodeling of cell adhesion by i) the phosphorylation of Focal Adhesion Kinase and ii) a modification of actin cytoskeleton and focal adhesion complexes. These events stimulate cell migration and invasion. In conclusion, our findings indicate that CRF2 signaling controls cellular organization and may promote metastatic potential of human CRC cells through an epithelial-mesenchymal transition like process. This contributes to the comprehension of the tumor-promoting effects of stress molecules and designates Ucn2/3-CRF2 tandem as a target to prevent CRC progression and aggressiveness. Public Library of Science 2013-11-18 /pmc/articles/PMC3832608/ /pubmed/24260200 http://dx.doi.org/10.1371/journal.pone.0079335 Text en © 2013 Ducarouge et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ducarouge, Benjamin
Pelissier-Rota, Marjolaine
Lainé, Michèle
Cristina, Nadine
Vachez, Yvan
Scoazec, Jean-Yves
Bonaz, Bruno
Jacquier-Sarlin, Muriel
spellingShingle Ducarouge, Benjamin
Pelissier-Rota, Marjolaine
Lainé, Michèle
Cristina, Nadine
Vachez, Yvan
Scoazec, Jean-Yves
Bonaz, Bruno
Jacquier-Sarlin, Muriel
CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells
author_facet Ducarouge, Benjamin
Pelissier-Rota, Marjolaine
Lainé, Michèle
Cristina, Nadine
Vachez, Yvan
Scoazec, Jean-Yves
Bonaz, Bruno
Jacquier-Sarlin, Muriel
author_sort Ducarouge, Benjamin
title CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells
title_short CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells
title_full CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells
title_fullStr CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells
title_full_unstemmed CRF2 Signaling Is a Novel Regulator of Cellular Adhesion and Migration in Colorectal Cancer Cells
title_sort crf2 signaling is a novel regulator of cellular adhesion and migration in colorectal cancer cells
description Stress has been proposed to be a tumor promoting factor through the secretion of specific neuromediators, such as Urocortin2 and 3 (Ucn2/3), however its role in colorectal cancer (CRC) remains elusive. We observed that Ucn2/3 and their receptor the Corticotropin Releasing Factor receptor 2 (CRF2) were up-regulated in high grade and poorly differentiated CRC. This suggests a role for CRF2 in the loss of cellular organization and tumor progression. Using HT-29 and SW620 cells, two CRC cell lines differing in their abilities to perform cell-cell contacts, we found that CRF2 signals through Src/ERK pathway to induce the alteration of cell-cell junctions and the shuttle of p120ctn and Kaiso in the nucleus. In HT-29 cells, this signaling pathway also leads to the remodeling of cell adhesion by i) the phosphorylation of Focal Adhesion Kinase and ii) a modification of actin cytoskeleton and focal adhesion complexes. These events stimulate cell migration and invasion. In conclusion, our findings indicate that CRF2 signaling controls cellular organization and may promote metastatic potential of human CRC cells through an epithelial-mesenchymal transition like process. This contributes to the comprehension of the tumor-promoting effects of stress molecules and designates Ucn2/3-CRF2 tandem as a target to prevent CRC progression and aggressiveness.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832608/
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