Class III β-tubulin counteracts the ability of paclitaxel to inhibit cell migration.

Class III β-tubulin counteracts the ability of paclitaxel to inhibit cell migration.
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DOI:
10.18632/oncotarget.250
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发表时间:
2011-05
期刊:
影响因子:
--
通讯作者:
Cabral F
Cabral F
中科院分区:
其他
文献类型:
--
作者:
Ganguly A;Yang H;Cabral F

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III类β-微管蛋白(β3)与肿瘤侵袭性、对治疗的抗性和患者复发相关。为了阐明其作用,我们测试了β3对细胞迁移的影响。β3在HeLa和MCF-7中的表达不改变细胞迁移的固有速率,但它阻止了低无毒浓度紫杉醇对迁移的抑制。在四环素调节β3表达的CHO细胞中证实了对细胞运动性的影响。细胞迁移和微管动力学被相似浓度的紫杉醇抑制,但当β3表达时需要5-10倍的药物浓度。紫杉醇组细胞迁移的方向性正常,但细胞处于“暂停”状态的时间更长,在此期间没有净移动。这些研究支持紫杉醇通过抑制微管动力学抑制细胞迁移和β3-微管蛋白通过维持微管动力学活性抵消紫杉醇作用的模型。结果为表达β3的肿瘤的侵袭性提供了潜在的解释。
Class III β-tubulin (β3) is associated with tumor aggressiveness, resistance to therapy, and patient relapse. To elucidate its action, we tested β3's effect on cell migration. Expression of β3 in HeLa and MCF-7 did not alter the intrinsic rate of cell migration, but it prevented the inhibition of migration by low, nontoxic concentrations of paclitaxel. The effects on cell motility were confirmed in CHO cells with tetracycline regulated expression of β3. Cell migration and microtubule dynamics were inhibited by similar concentrations of paclitaxel, but required a 5-10 fold higher drug concentration when β3 was expressed. The directionality of migration was normal in paclitaxel, but cells spent more time in a “paused” state during which there was no net movement. These studies support a model in which paclitaxel inhibits cell migration by suppressing microtubule dynamics and β3-tubulin counteracts paclitaxel action by maintaining microtubule dynamic activity. The results provide a potential explanation for the aggressiveness of β3-expressing tumors.
DOI: 10.1158/1535-7163.mct-10-0552
发表时间: 2010-11
影响因子: 5.7
作者:
Ganguly A;Yang H;Cabral F
通讯作者: Cabral F
体内微管是可用的β-微管蛋白同种型的共聚物:使用合成肽抗原引起的多克隆抗体的六个脊椎动物β-微管蛋白同种型的定位。
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