title: Alpha2beta1 integrin promotes T cell survival and migration through the concomitant activation of ERK/Mcl-1 and p38 MAPK pathways.
abstract: Integrin-mediated attachment to extracellular matrix (ECM) is crucial for cancer progression. Malignant T cells such as acute lymphoblastic leukemia (T-ALL) express β1 integrins, which mediate their interactions with ECM. However, the role of these interactions in T-ALL malignancy is still poorly explored. In the present study, we investigated the effect of collagen; an abundant ECM, on T-ALL survival and migration. We found that collagen through α2β1 integrin promotes the survival of T-ALL cell lines in the absence of growth factors. T-ALL cell survival by collagen is associated with reduced caspase activation and maintenance of Mcl-1 levels. Collagen activated both ERK and p38 MAPKs but only MAPK/ERK was required for collagen-induced T-ALL survival. However, we found that α2β1 integrin promoted T-ALL migration via both ERK and p38. Together these data indicate that α2β1 integrin signaling can represent an important signaling pathway in T-ALL pathogenesis and suggest that its blockade could be beneficial in T-ALL treatment.
authors.affiliation: Centre de recherche du CHU de Québec, Axe des maladies infectieuses et immunitaires, Département de Microbiologie-Immunologie, Faculté de Médecine, Université Laval, Québec, Canada.
authors.forename: Dalila
authors.initials: D
authors.lastname: Naci
authors.affiliation: Centre de recherche du CHU de Québec, Axe des maladies infectieuses et immunitaires, Département de Microbiologie-Immunologie, Faculté de Médecine, Université Laval, Québec, Canada. Electronic address: fawzi.aoudjit@crchul.ulaval.ca.
authors.forename: Fawzi
authors.initials: F
authors.lastname: Aoudjit
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D019169:Jurkat Cells; D059630:Mesenchymal Stem Cells / Q000166:cytology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D038982:Integrin alpha2beta1; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D034741:RNA, Small Interfering; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9
keywords: ERK; Mcl-1; Migration; Survival; p38; α2β1 integrin