耶魯大學(xué)的研究表明壓力會產(chǎn)生促使細(xì)胞演變成腫瘤的信號,。發(fā)表于《自然》雜志上的這項研究成果描述了癌癥控制人體的一種全新的途徑,，同時也向科學(xué)家們提示了制服這種致命疾病的新方法,。
迄今為止,，大部分研究者都相信只有當(dāng)單個細(xì)胞內(nèi)發(fā)生一個以上的致癌突變時才能促使腫瘤生長?？墒?，由遺傳學(xué)教授兼副主任許田領(lǐng)導(dǎo)的耶魯研究小組以及霍華德·休斯醫(yī)學(xué)研究所 (Howard Hughes Medical Institute) 研究員通過研究證明致癌突變在促進腫瘤的發(fā)展時會共同作用，即使當(dāng)它們存在于同一組織的不同細(xì)胞內(nèi)時也是如此,。
“這無疑是個壞消息,，因為在某個組織的不同細(xì)胞內(nèi)積累突變要比在同一個細(xì)胞內(nèi)積累突變?nèi)菀椎枚啵?rdquo;同時也是耶魯癌癥中心 (Yale Cancer Center) 和位于中國復(fù)旦大學(xué)內(nèi)的復(fù)旦-耶魯生物醫(yī)學(xué)研究中心 (Fudan-Yale Center for Biomedical Research) 研究員的許田表示。
耶魯?shù)难芯啃〗M以果蠅為對象,，研究了目前已知和人類癌癥發(fā)展有關(guān)的兩種基因的活動情況：一種是被稱為RAS的基因，它牽涉到30%的癌癥,；另一種是叫做scribble的抑癌基因,，它在發(fā)生突變時會促進腫瘤的發(fā)展。單獨的變異RAS基因和有缺陷的scribble基因都不會導(dǎo)致癌癥,。許田實驗室內(nèi)的研究員們先前已經(jīng)證明同一細(xì)胞內(nèi)兩種基因的結(jié)合即可能誘發(fā)惡性腫瘤,。
不過，耶魯?shù)难芯啃〗M發(fā)現(xiàn)這些突變并不一定要同時存在于同一個細(xì)胞內(nèi)才會導(dǎo)致腫瘤,。只存在變異RAS的細(xì)胞在其旁邊的細(xì)胞內(nèi)存在有缺陷的scribble基因時也可能會發(fā)展成惡性腫瘤,。他們還發(fā)現(xiàn)諸如創(chuàng)傷之類的壓力情況也會誘發(fā)癌癥的形成。例如,，當(dāng)組織內(nèi)發(fā)生創(chuàng)傷時RAS細(xì)胞就會演變成腫瘤 ,。肇事原因就在于兩種現(xiàn)象都會導(dǎo)致被稱為JNK的信號產(chǎn)生過程，而這一過程會受到環(huán)境壓力情況的激發(fā),。
“有許多不同的情況能夠觸發(fā)壓力信號：身體壓力,、情感壓力、感染,、炎癥等等,。這是又一個關(guān)于癌癥的壞消息”許田補充道。
論文在說明癌癥要比人們先前所了解的更容易在人體內(nèi)發(fā)生的同時也確定了在發(fā)達世界內(nèi)預(yù)防和治療這種最致命疾病之一的新目標(biāo),。耶魯?shù)难芯啃〗M發(fā)現(xiàn) JNK 壓力信號會從一個細(xì)胞傳遞到另一個細(xì)胞,，但是這種傳播過程也是能夠被阻斷的,。（生物谷Bioon.com）
壓力與健康：
J. Neurosci：短期壓力就能損害學(xué)習(xí)和記憶力
JCI：與壓力導(dǎo)致的高血壓相關(guān)的基因
PNAS：家長壓力大易誘發(fā)孩子哮喘
AIM：中風(fēng)與工作壓力大有關(guān)
FASEB J：心理壓力會讓你的頭發(fā)變白嗎？
生物谷推薦原始出處：
Nature advance online publication 13 January 2010 | doi:10.1038/nature08702
Interaction between Ras V12 and scribbled clones induces tumour growth and invasion
Ming Wu1,3, José Carlos Pastor-Pareja1,3 & Tian Xu1,2
1 Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06519, USA
2 Fudan-Yale Biomedical Research Center, Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan University, 220 Han Dan Road, Shanghai 20043, China
3 These authors contributed equally to this work.
Correspondence to: Tian Xu1,2 Correspondence and requests for materials should be addressed to T.X.
Human tumours have a large degree of cellular and genetic heterogeneity1. Complex cell interactions in the tumour and its microenvironment are thought to have an important role in tumorigenesis and cancer progression2. Furthermore, cooperation between oncogenic genetic lesions is required for tumour development3; however, it is not known how cell interactions contribute to oncogenic cooperation. The genetic techniques available in the fruitfly Drosophila melanogaster allow analysis of the behaviour of cells with distinct mutations4, making this the ideal model organism with which to study cell interactions and oncogenic cooperation. In Drosophila eye-antennal discs, cooperation between the oncogenic protein Ras V12 (ref. 5) and loss-of-function mutations in the conserved tumour suppressor scribbled (scrib)6, 7 gives rise to metastatic tumours that display many characteristics observed in human cancers8, 9, 10, 11. Here we show that clones of cells bearing different mutations can cooperate to promote tumour growth and invasion in Drosophila. We found that the Ras V12 and scrib- mutations can also cause tumours when they affect different adjacent epithelial cells. We show that this interaction between Ras V12 and scrib- clones involves JNK signalling propagation and JNK-induced upregulation of JAK/STAT-activating cytokines, a compensatory growth mechanism for tissue homeostasis. The development of Ras V12 tumours can also be triggered by tissue damage, a stress condition that activates JNK signalling. Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers.
