Silencing Focal Adhesion Kinase in B Cell Leukemia Decreases Cell Survival and Increases Drug Sensit

• 作 者: YiLe;LeslieE.Silberstein;
• 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(
• 发表日期: 2008年期

　　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.