【摘 要】
：
Focal Adhesion Kinase (FAK) is expressed and activated at higher levels in malignant cells than in normal cells.Previously we reported that FAK knockdown in B-ALL cells causes impaired chemotactic and
【机 构】
：
Center of Human Cell Therapy Children's Hospital and Immune Disease Institute Harvard Medical Schoo
【出 处】
：
BIT Life Sciences 1st Annual World Cancer Congess-2008(2008中
论文部分内容阅读
Focal Adhesion Kinase (FAK) is expressed and activated at higher levels in malignant cells than in normal cells.Previously we reported that FAK knockdown in B-ALL cells causes impaired chemotactic and pro-adhesive responses to CXCL12 (Glodek et al.Leukemia 2007).Here, we demonstrate that FAK is highly tyrosine phosphorylated in B cells from 7 B-lineage chronic lymphocytic leukemia (B-CLL) and 9 B-lineage acute lymphoblast leukemia (BALL) patients, while FAK is not phosphorylated in B cells from healthy individuals.After screening the SiRNA target sites of FAK, we found that one site can knock down 95% of FAK proteins in pro-B and pre-B cell lines.Knock down of FAK by SiRNA reduces cell migration.Significantly, SiRNA-FAK pro-B REH cells undergo 5-fold higher caspase-3 dependent apoptosisin response to predinisolone than wild type REH cells.Data from confocal microscopy and biochemistry show that SiRNA-FAK significantly reduced mitochondrial membrane potential and integrity, suggesting that FAK proteins increases drug resistance of leukemia cells by protecting mitochondrial membrane.Taken together, FAK is highly activated in B cell leukemia and knock down of FAK by SiRNA causes compromised cell growth and increases drug sensitivity of B-ALL cells.Thus, targeting FAK by SiRNA should be explored for its potential as an effective anti-leukemic therapeutic modality.
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