近日,，諾丁漢大學(xué)的研究者們發(fā)現(xiàn)一種存在于低等水蠕蟲中的基因可能在癌癥發(fā)展中起著重要的作用,。來自醫(yī)學(xué)研究理事會(huì)(MRC)的專家們發(fā)現(xiàn)取出蠕蟲中的SMG-1基因會(huì)導(dǎo)致正常細(xì)胞分裂失控,，造成包括腫瘤在內(nèi)的致命疾病的突然惡化。
此項(xiàng)研究的帶頭人,， 生物學(xué)院的Aziz Aboobaker博士稱,，SMG-1基因可能會(huì)扮演阻止生物生長(zhǎng)的角色。如果在人類身上也適用,，它將會(huì)被研制成治療癌癥和其他衰老病癥的藥劑,。同時(shí)，這種低等蠕蟲可被用作普遍使用的研究人類疾病的模型,。此研究由醫(yī)學(xué)研究理事會(huì)和生物科學(xué)研究理事會(huì)(BBSRC)共同資助,。研究成果已刊登在《公共科學(xué)圖書館遺傳學(xué)》PLoS Genetics期刊上。
Aboobaker博士說：“越來越多的證據(jù)證明一些同類的基因可調(diào)節(jié)傷口愈合和再生,，衰老以及癌癥,。渦蟲提供了一個(gè)研究所有這些問題的很好的模型。他們似乎繞過了普通的老化過程并在其嚴(yán)格控制下從干細(xì)胞分裂開始重新再造自己身體的某部分,，甚至包括它們的頭部,。我們已經(jīng)發(fā)現(xiàn)眾所周知的動(dòng)物生長(zhǎng)調(diào)節(jié)器 - SMG-1基因和mTOR信號(hào)通路配合默契地進(jìn)行對(duì)渦蟲生長(zhǎng)和再生的嚴(yán)格控制。最重要的是,，如果把這種控制移出,，我們就會(huì)看見活躍的細(xì)胞分裂和腫瘤的形成，這將最終至蠕蟲于死地,。這說明了SMG-1基因是一種我們之前未知的抑制腫瘤發(fā)展的基因,。”
研究者們相信SMG-1基因扮演著抑制mTOR信號(hào)通路的角色，以致于導(dǎo)致人類癌癥以及其他與衰老相關(guān)病癥的惡化,。這樣一來,，存在癌癥患者中的SMG-1基因就會(huì)發(fā)生突變。已經(jīng)有研究證明突變的SMG-1基因存在于癌癥患者身上?，F(xiàn)在的研究需進(jìn)一步探討這些突變是否導(dǎo)致非正常細(xì)胞的生長(zhǎng),，以促發(fā)癌癥的惡化,。
醫(yī)學(xué)研究理事會(huì)針對(duì)干細(xì)胞研究，發(fā)育生物學(xué)和再生醫(yī)學(xué)的項(xiàng)目負(fù)責(zé)人Paul Colville-Nash說：“這項(xiàng)研究是關(guān)于低等蠕蟲如何為我們深入研究人類衛(wèi)生與疾病提供新線索的典型,。最終它將成為癌癥等疾病的新型治療方法,。渦蟲是自由生活的非寄生扁蟲。它廣泛分布于自然界,，并有一些顯著的特點(diǎn) – 如可再生肌肉,，皮膚,，內(nèi)臟,，甚至整個(gè)大腦，不斷循環(huán) ,。它們也因此被科學(xué)家們稱為“不老神仙”,。（生物谷Bioon.com）
doi:10.1371/journal.pgen.1002619
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SMG-1 and mTORC1 Act Antagonistically to Regulate Response to Injury and Growth in Planarians
Cristina González-Estévez1*, Daniel A. Felix1, Matthew D. Smith1, Jordi Paps2, Simon J. Morley3, Victoria James4, Tyson V. Sharp4, A. Aziz Aboobaker1*
Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth and the formation of regenerative blastemas that remain undifferentiated and that lead to lethal ectopic outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and differentiation defects are hallmarks of this uncontrolled growth. These data imply a previously unappreciated and novel physiological function for this PIKK family member. In contrast we found that planarian members of the mTOR complex 1, tor and raptor, are required for the initial response to injury and blastema formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal growth requires mTOR signalling. We also found that the macrolide rapamycin, a natural compound inhibitor of mTORC1, is able to increase the survival rate of smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model where Smg-1 acts as a novel regulator of both the response to injury and growth control mechanisms. Our data suggest the possibility that this may be by suppressing mTOR signalling. Characterisation of both the planarian mTORC1 signalling components and another PIKK family member as key regulators of regeneration and growth will influence future work on regeneration, growth control, and the development of anti-cancer therapies that target mTOR signalling.
