美國和澳大利亞科學(xué)家近日研究發(fā)現(xiàn)，果蠅成體干細(xì)胞內(nèi)的一種分子信使就像城堡的崗哨一樣,，當(dāng)感覺到癌癥入侵風(fēng)險(xiǎn)的時(shí)候，會(huì)發(fā)出警報(bào),。隨后,，細(xì)胞分裂被中止，防止了細(xì)胞分裂失控及腫瘤的形成,。相關(guān)論文10月15日在線發(fā)表于《自然》（Nature）雜志上,。
美國密歇根大學(xué)生命科學(xué)研究所的Yukiko Yamashita和同事以果蠅作為實(shí)驗(yàn)對象，研究發(fā)現(xiàn),，細(xì)胞分裂部分由中心體（centrosome）控制,，它提供了有助引導(dǎo)染色體分散到子細(xì)胞中的框架。正常情況下,，中心體與臨近的信使細(xì)胞相垂直,，而當(dāng)中心體出現(xiàn)不正確定位，就會(huì)破壞有絲分裂機(jī)器，使其朝向干細(xì)胞過度增殖和癌癥方向進(jìn)行,。
檢查站機(jī)制能感覺到中心體的偏離,，隨后拉響警報(bào)，終止細(xì)胞分裂,，阻止癌癥入侵,。Yamashita說：“我們的研究顯示，為了阻止會(huì)導(dǎo)致癌癥的異常細(xì)胞增殖,，干細(xì)胞發(fā)展出了這種自我檢查系統(tǒng),，我們稱作‘檢查站’。如果一個(gè)細(xì)胞看起來要以錯(cuò)誤的方式分裂,，檢查站就會(huì)感覺到并發(fā)出信號(hào)：‘別分裂,！別分裂！’,。”
但是存在一個(gè)平衡問題：如果檢查站機(jī)制將細(xì)胞分裂降低到極低程度,，那么就會(huì)缺乏新細(xì)胞，從而加速組織的衰老,。她說：“衰老是過少的分裂,，而癌癥是過多的分裂，人們長期以來推測一定有程序控制著二者的平衡,。我們可能發(fā)現(xiàn)了維持會(huì)導(dǎo)致癌癥的過度增殖和衰老之間精致平衡的機(jī)制,。”
如果人類具有相似的檢查站機(jī)制并且將來能被研究人員利用的話，我們就能調(diào)整細(xì)胞分裂的速度,，來控制腫瘤形成以及組織衰老,。不過Yamashita強(qiáng)調(diào)，現(xiàn)在尚無類似的哺乳動(dòng)物研究,，談人類應(yīng)用還為時(shí)過早,。
Yamashita說：“這是一把雙刃劍，兩面均可傷人,。一條路徑導(dǎo)致癌癥,，另一條則會(huì)導(dǎo)致衰老，而我們尚未找到能避免衰老且不會(huì)罹患癌癥的方法,。”（生物谷Bioon.com）
生物谷推薦原始出處：
Nature,，doi:10.1038/nature07386,，Jun Cheng,，Yukiko M. Yamashita
Centrosome misorientation reduces stem cell division during ageing
Jun Cheng1,5, Nezaket Türkel2,5,6, Nahid Hemati2,5, Margaret T. Fuller4, Alan J. Hunt1 & Yukiko M. Yamashita2,3
Department of Biomedical Engineering, Center for Ultrafast Optical Science
Life Sciences Institute, Center for Stem Cell Biology,
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of Developmental Biology and Genetics, Stanford University, School of Medicine, Stanford, California 94305, USA
These authors contributed equally to this work.
Present address: Peter MacCallum Cancer Centre, Anatomy and Cell Biology Department, University of Melbourne, Melbourne, Victoria 3002, Australia.
Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila. Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.
