title: p38 and JNK pathways control E-selectin-dependent extravasation of colon cancer cells by modulating miR-31 transcription.
abstract: Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to vascular endothelial cells. It requires the interaction between adhesion receptors such as E-selectin present on endothelial cells and their ligands on cancer cells. Notably, E-selectin influences the metastatic potential of breast, bladder, gastric, pancreatic, and colorectal carcinoma as well as of leukemia and lymphoma. Here, we show that E-selectin expression induced by the pro-inflammatory cytokine IL-1β is directly and negatively regulated by miR-31. The transcription of miR-31 is activated by IL-1β. This activation depends on p38 and JNK MAP kinases, and their downstream transcription factors GATA2, c-Fos and c-Jun. The miR-31-mediated repression of E-selectin impairs the metastatic potential of colon cancer cells by decreasing their adhesion to, and migration through, the endothelium. These results highlight for the first time that microRNA mediates E-selectin-dependent extravasation of colon cancer cells.
authors.affiliation: St-Patrick Research Group in Basic Oncology, CHU de Québec-Université Laval Research Centre (Hôtel-Dieu de Québec), Laval University Cancer Research Centre, Quebec City, Québec, G1R 2J6, Canada.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: St-Patrick Research Group in Basic Oncology, CHU de Québec-Université Laval Research Centre (Hôtel-Dieu de Québec), Laval University Cancer Research Centre, Quebec City, Québec, G1R 2J6, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Simoneau
authors.affiliation: St-Patrick Research Group in Basic Oncology, CHU de Québec-Université Laval Research Centre (Hôtel-Dieu de Québec), Laval University Cancer Research Centre, Quebec City, Québec, G1R 2J6, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Huot
authors.affiliation: St-Patrick Research Group in Basic Oncology, CHU de Québec-Université Laval Research Centre (Hôtel-Dieu de Québec), Laval University Cancer Research Centre, Quebec City, Québec, G1R 2J6, Canada.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Simard
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D019040:E-Selectin / Q000378:metabolism*; D042783:Endothelial Cells / Q000502:physiology; D050989:GATA2 Transcription Factor / Q000378:metabolism; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009360:Neoplastic Cells, Circulating; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D019040:E-Selectin; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: GATA2; IL-1β metastasis; c-Fos; c-Jun; endothelial cells