title: Enhanced adhesion/migration and induction of Pyk2 expression in K562 cells following imatinib exposure.
abstract: Concern about extramedullary relapse (EMR) despite favorable response in the bone marrow has been raised with the use of imatinib for treatment of chronic myeloid leukemia (CML). In the present study we show an increase in adhesion, migration and invasion capabilities of the CML cell line K562 following imatinib administration. Imatinib induced upregulation of Pyk2 mRNA and protein levels. Pyk2 inhibition resulted in a reduction of K562 cells' adhesion and migration subsequent to imatinib treatment. This effect was similar to that shown by us previously with all trans retinoic acid (ATRA) in the acute promyelocytic leukemia (APL) cell line NB4. Our data pinpoint Pyk2 as a shared key mediator of targeted-therapy induced adhesion and migration and may implicate that targeting Pyk2 may serve as an effective therapeutic strategy to reduce EMR in APL and CML.
authors.affiliation: Felsenstein Medical Research Center, Beilinson Hospital, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Adelina
authors.initials: A
authors.lastname: Ovcharenko
authors.forename: Galit
authors.initials: G
authors.lastname: Granot
authors.forename: Oshrat Hershkovitz
authors.initials: OH
authors.lastname: Rokah
authors.forename: Jennifer
authors.initials: J
authors.lastname: Park
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D051418:Focal Adhesion Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D034741:RNA, Small Interfering; D000068877:Imatinib Mesylate; D051418:Focal Adhesion Kinase 2
keywords: Adhesion; Chronic myeloid leukemia; Extramedullary disease; Imatinib; Migration; Pyk2