title: CRF2 signaling is a novel regulator of cellular adhesion and migration in colorectal cancer cells.
abstract: 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.
authors.affiliation: Equipe du Stress et des Interactions Neurodigestives, INSERM U836, Grenoble, France ; Université Joseph Fourier, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ducarouge
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Pelissier-Rota
authors.forename: Michèle
authors.initials: M
authors.lastname: Lainé
authors.forename: Nadine
authors.initials: N
authors.lastname: Cristina
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vachez
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonaz
authors.forename: Muriel
authors.initials: M
authors.lastname: Jacquier-Sarlin
mesh_terms: D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D016133:Polymerase Chain Reaction; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone