title: Localized translation regulates cell adhesion and transendothelial migration.
abstract: Epithelial-to-mesenchymal transition (EMT) is a process by which cancer cells gain the ability to leave the primary tumor site and invade surrounding tissues. These metastatic cancer cells can further increase their plasticity by adopting an amoeboid-like morphology, by undergoing mesenchymal-to-amoeboid transition (MAT). We found that adhering cells produce spreading initiation centers (SICs), transient structures that are localized above nascent adhesion complexes, and share common biological and morphological characteristics associated with amoeboid cells. Meanwhile, spreading cells seem to return to a mesenchymal-like morphology. Thus, our results indicate that SIC-induced adhesion recapitulates events  that are associated with amoeboid-to-mesenchymal transition (AMT). We found that polyadenylated RNAs are enriched within SICs, blocking their translation decreased adhesion potential of metastatic cells that progressed through EMT. These results point to a so-far-unknown checkpoint that regulates cell adhesion and allows metastatic cells to alter adhesion strength to modulate their dissemination.
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada, G1V 0A6.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bergeman
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada, G1V 0A6.
authors.forename: Alexia
authors.initials: A
authors.lastname: Caillier
authors.affiliation: CRCHU de Québec: Hôtel-Dieu de Québec, Québec, Canada G1R 3S3.
authors.forename: François
authors.initials: F
authors.lastname: Houle
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada, G1V 0A6.
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Gagné
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada, G1V 0A6 marc-etienne.huot@crchuq.ulaval.ca.|CRCHU de Québec: Hôtel-Dieu de Québec, Québec, Canada G1R 3S3.
authors.forename: Marc-Étienne
authors.identifier: 0000-0001-5155-5338
authors.initials: MÉ
authors.lastname: Huot
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D048430:Cell Shape; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D022001:Focal Adhesions / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D008954:Models, Biological; D009362:Neoplasm Metastasis; D026723:Polyadenylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020558:GTP Phosphohydrolases
keywords: AMT; Amoeboid-to-mesenchymal transition; EMT; Epithelial cells; Epithelial-to-mesenchymal transition; Focal adhesion; Invasion; MAT; Mesenchymal cells; Mesenchymal-to-amoeboid transition; RNA-binding proteins; SICs; Spreading initiation centers; Translation regulation