Changes in cell adhesivity and cytoskeleton-related proteins during imatinib-induced apoptosis of leukemic JURL-MK1 cells.
The fusion protein Bcr-Abl, which is the molecular cause of chronic myelogenous leukemia (CML) interacts in multiple points with signaling pathways regulating the cellular adhesivity and cytoskeleton architecture and dynamics. We explored the effects of imatinib mesylate, an inhibitor of Bcr-Abl protein used in front-line CML therapy, on the adhesivity of JURL-MK1 cells to fibronectin and searched for underlying changes in the cell proteome. As imatinib induces apoptosis of JURL-MK1 cells, we used three different caspase inhibitors to discriminate between direct consequences of Bcr-Abl inhibition and secondary changes related to the apoptosis. Imatinib treatment caused a transient increase in JURL-MK1 cell adhesivity to fibronectin, possibly due to the switch off of Bcr-Abl activity. Subsequently, we observed a number of changes including a decrease in cell adhesivity, F-actin decomposition, reduction of integrin β1, CD44, and paxillin expression levels and a marked increase in cofilin phophorylation at Ser3. These events were generally related to the proceeding apoptosis but they differed in their sensitivity to the individual caspase inhibitors.
Kuželová
K
K
Department of Cellular Biochemistry, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. kuzel@uhkt.cz
Pluskalová
M
M
Grebeňová
D
D
Pavlásková
K
K
Halada
P
P
Hrkal
Z
Z
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D051419:Paxillin / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014335:Tropomyosin / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D005353:Fibronectins; D051419:Paxillin; D010879:Piperazines; D011743:Pyrimidines; D014335:Tropomyosin; D000068877:Imatinib Mesylate