Cell：保护细胞纤毛可抑制癌细胞扩散
生物谷报道： 一项最新的研究发现，与癌症扩散即转移相关的蛋白质能导致从细胞延伸出来的类似毛发的结构（即纤毛）降解。这种“脱发”可以导致失控的细胞分裂。研究人员推测，能保护纤毛的药物可能有助于抑制癌症的扩散。这项研究的结果刊登在最新一期的Cell杂志上。
支气管中，中央部份, 你还能看到未受破坏的细胞纤毛, 但是在周围的已经被烟草烧焦不存在了
身体中许多细胞都有纤毛：肺脏细胞具有大量的能有节奏的运转来移动黏液的纤毛；存在于心脏、大脑和肾脏等器脏内的一些其他细胞则具有一个原始的纤毛，这种纤毛被认为具有与天线一样接受化学信号的功能。
一些初步的证据显示，这种纤毛含有能硬性细胞增殖的化学物质的受体。现在，研究人员已经发现了以纤毛为基础的信号途径与癌症的密切关系。
来自美国费城Fox Chase癌症研究中心的Elizabeth Henske和同学对来自眼睛后面的人类细胞进行了研究。这些细胞通常都具有纤毛。
利用荧光标志物，他们发现当细胞分裂开始时，一种特殊的蛋白质突然出现在纤毛基部，并在数分钟内将纤毛结构溶解掉。这种蛋白质叫做Aurora A，它的出现似乎能促进肿瘤的扩散。据研究人员介绍，Aurora A的过度活跃有时会导致细胞永久性地失去它们的“天线”，并因为无法接收到终止细胞分裂的信号而导致癌变。
Henske指出，癌变的肾脏细胞缺少纤毛。她推测，能抑制Aurora A的药物可能有助于阻止肿瘤的转移。
原始出处:
Cell, Vol 129, 1351-1363, 29 June 2007
Article
HEF1-Dependent Aurora A Activation Induces Disassembly of the Primary Cilium
Elena N. Pugacheva,1 Sandra A. Jablonski,1 Tiffiney R. Hartman,2 Elizabeth P. Henske,2 and Erica A. Golemis1,
1 Division of Basic Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
2 Division of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Corresponding author
Erica A. Golemis
ea_golemis@fccc.edu
Summary
The mammalian cilium protrudes from the apical/lumenal surface of polarized cells and acts as a sensor of environmental cues. Numerous developmental disorders and pathological conditions have been shown to arise from defects in cilia-associated signaling proteins. Despite mounting evidence that cilia are essential sites for coordination of cell signaling, little is known about the cellular mechanisms controlling their formation and disassembly. Here, we show that interactions between the prometastatic scaffolding protein HEF1/Cas-L/NEDD9 and the oncogenic Aurora A (AurA) kinase at the basal body of cilia causes phosphorylation and activation of HDAC6, a tubulin deacetylase, promoting ciliary disassembly. We show that this pathway is both necessary and sufficient for ciliary resorption and that it constitutes an unexpected nonmitotic activity of AurA in vertebrates. Moreover, we demonstrate that small molecule inhibitors of AurA and HDAC6 selectively stabilize cilia from regulated resorption cues, suggesting a novel mode of action for these clinical agents.
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