Adhesion structures in leukemia cells and their regulation by Src family kinases
| Autor: | Dana Grebeňová, Pavla Röselová, Aleš Holoubek, Kateřina Kuželová, Adam Obr |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Integrin Dasatinib Focal adhesion 03 medical and health sciences Cellular and Molecular Neuroscience LYN hemic and lymphatic diseases medicine Cell Adhesion Humans Progenitor cell Phosphorylation Cell adhesion Focal Adhesions Leukemia biology Cell Biology medicine.disease Cell biology Fibronectins Haematopoiesis 030104 developmental biology src-Family Kinases Focal Adhesion Protein-Tyrosine Kinases biology.protein Proto-oncogene tyrosine-protein kinase Src Research Paper |
| DOI: | 10.6084/m9.figshare.5176972.v1 |
| Popis: | Interaction of leukemia blasts with the bone marrow extracellular matrix often results in protection of leukemia cells from chemotherapy and in persistence of the residual disease which is on the basis of subsequent relapses. The adhesion signaling pathways have been extensively studied in adherent cells as well as in mature haematopoietic cells, but the adhesion structures and signaling in haematopoietic stem and progenitor cells, either normal or malignant, are much less explored. We analyzed the interaction of leukemia cells with fibronectin (FN) using interference reflection microscopy, immunofluorescence, measurement of adherent cell fraction, real-time microimpedance measurement and live cell imaging. We found that leukemia cells form very dynamic adhesion structures similar to early stages of focal adhesions. In contrast to adherent cells, where Src family kinases (SFK) belong to important regulators of focal adhesion dynamics, we observed only minor effects of SFK inhibitor dasatinib on leukemia cell binding to FN. The relatively weak involvement of SFK in adhesion structure regulation might be associated with the lack of cytoskeletal mechanical tension in leukemia cells. On the other hand, active Lyn kinase was found to specifically localize to leukemia cell adhesion structures and a less firm cell attachment to FN was often associated with higher Lyn activity (this unexpectedly occurred also after cell treatment with the inhibitor SKI-1). Lyn thus may be important for signaling from integrin-associated complexes to other processes in leukemia cells. |
| Databáze: | OpenAIRE |
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