p130Cas acts as survival factor during PMA-induced apoptosis in HL-60 promyelocytic leukemia cells.

p130Cas acts as survival factor during PMA-induced apoptosis in HL-60 promyelocytic leukemia cells.
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DOI:
10.1016/j.biocel.2012.12.017
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发表时间:
2013-03
期刊:
The international journal of biochemistry & cell biology
影响因子:
--
通讯作者:
Kirsch KH
Kirsch KH
中科院分区:
其他
文献类型:
--
作者:
Kumbrink J;Kirsch KH

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佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)通过诱导粘附、细胞聚集和凋亡来刺激早幼粒白血病HL-60细胞分化。p130 Cas(Crk相关底物)是控制细胞生长、附着和凋亡程序的接头分子。值得注意的是,p130 Cas活性升高与白血病和淋巴瘤相关。由于p130 Cas调节细胞粘附,我们测试了它参与造血细胞分化的假设。在这里,我们表明,PMA介导的晚期诱导HL-60细胞中的p130 Cas的表达,这与细胞聚集和凋亡的发生相一致。异位p130 Cas表达导致细胞粘附增加和早期细胞聚集,这可能有助于在这些转导子中观察到的细胞活力增加。p130 Cas表达与其自身调节因子EGR 1、其辅助调节因子NAB 2和凋亡的诱导同时发生。抑制PMA处理的HL-60细胞中的NF-κ B可促进细胞聚集的丧失和细胞死亡。我们进一步显示PMA处理期间,NF-κ B抑制导致p130 Cas、EGFR 1和NAB 2水平降低。因此,p130 Cas通过限制PMA介导的细胞簇破坏和导致的HL-60细胞中的细胞死亡而充当存活因子。
Phorbol 12-myristate 13-acetate (PMA) stimulates the differentiation of promyelocytic leukemia HL-60 cells by inducing adhesion followed by cell aggregation and, importantly, apoptosis. p130Cas (Crk-associated substrate) is an adapter molecule that controls cell growth, attachment and apoptotic programs. Notably, elevated p130Cas activity is associated with leukemias and lymphomas. Since p130Cas regulates cell adhesion, we tested the hypothesis that it participates in the differentiation of hematopoietic cells. Here we show that PMA mediates the late induction of p130Cas expression in HL-60 cells, which coincided with cell aggregation and the onset of apoptosis. Ectopic p130Cas expression led to increased cell adhesion and earlier cell aggregation potentially contributing to the observed increased cell viability in these transductants. p130Cas expression concurred with the induction of its own regulator the transcription factor EGR1, its coregulator NAB2, and apoptosis. NF-κ B inhibition in PMA-treated HL-60 cells promoted the loss of cell aggregation and cell death. We further showed a reduction of p130Cas, EGR1, and NAB2 levels in response to NF-κ B inhibition during PMA treatment. Hence, p130Cas acts as survival factor by limiting PMA-mediated cell cluster disruption and resulting cell death in HL-60 cells.
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