Alpha2beta1 integrin promotes T cell survival and migration through the concomitant activation of ERK/Mcl-1 and p38 MAPK pathways

• Published in: Cellular signalling 2014-09, Vol.26 (9), p.2008-2015
• Main Authors: Naci, Dalila, Aoudjit, Fawzi
• Format: Article
• Language: English
• Subjects: Activation; Apoptosis - drug effects; Bone Marrow Cells - cytology; Caspase 3 - metabolism; Caspase 9 - metabolism; Cell Survival - drug effects; Cellular; Coculture Techniques; Collagen - pharmacology; Collagens; Electrochemical machining; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; Humans; Integrin alpha2beta1 - metabolism; Jurkat Cells; Mcl-1; Mesenchymal Stromal Cells - cytology; Migration; Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; p38; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Pathways; RNA Interference; RNA, Small Interfering - metabolism; Signal Transduction - drug effects; Signalling; Survival; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; α2β1 integrin
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2014.05.016

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. •α2β1 integrin promotes leukemic T cell survival and migration on collagen.•Collagen anti-apoptotic effect is dependent on MAPK/ERK/Mcl-1 pathway.•Both ERK and p38 pathways are required for α2β1 integrin-induced cell migration.