俄勒岡州立大學(xué)研究員最新研究結(jié)果顯示,，在多種人類(lèi)癌癥含量都有所上升的一種酶,，似乎與果蠅的異常腫瘤生長(zhǎng)有關(guān)。這項(xiàng)發(fā)現(xiàn)為厘清清干細(xì)胞生物特征和癌癥之間的關(guān)系,，提供了一個(gè)新模型,。研究結(jié)果刊登于12月20日的Genes & Development中，第一作者為Ryan O. Andersen和博士后研究員Cheng-Yu Lee,。
研究小組利用熒光著色和激光掃描顯微鏡,，研究aurora-A基因的各種突變形式,，觀察其蛋白表達(dá)的變化怎樣影響果蠅成神經(jīng)細(xì)胞（neuroblasts）的功能。成神經(jīng)細(xì)胞是一種神經(jīng)干細(xì)胞,，保持干細(xì)胞的特征,，卻不會(huì)發(fā)展為腫瘤。
霍華德修斯醫(yī)學(xué)研究所的研究人員Chris Doe,，追蹤果蠅過(guò)量新生的成神經(jīng)細(xì)胞,，找到罪魁禍?zhǔn)?mdash;—aurora-A激酶。正常條件下aurora-A激酶如同一個(gè)交通警察,，在成神經(jīng)細(xì)胞有絲分裂過(guò)程中,，管理各種蛋白。
aurora-A在進(jìn)化過(guò)程中被保留了下來(lái),。Doe研究小組發(fā)現(xiàn)果蠅aurora-A突變會(huì)引發(fā)兩個(gè)明顯問(wèn)題：向神經(jīng)元分化有關(guān)的蛋白 （Numb）和成神經(jīng)干細(xì)胞自我更新（aPKC）會(huì)改變它們?cè)诩?xì)胞中的位置,，提供皮層極性的有絲分裂軸方向偏離，很快地導(dǎo)致攜帶錯(cuò)誤蛋白的新細(xì)胞大量增生,，導(dǎo)致腦瘤形成,。因此研究人員推測(cè)，aurora-A激酶在成神經(jīng)細(xì)胞中是調(diào)節(jié)蛋白位置所必需的,，如果沒(méi)有它,，向新生的神經(jīng)元傳遞的促神經(jīng)元蛋白質(zhì)的量會(huì)變得很少，新生的神經(jīng)元不會(huì)失去干細(xì)胞的特性,，導(dǎo)致果蠅腦中出現(xiàn)干細(xì)胞腫瘤,。
這項(xiàng)研究結(jié)果顛覆了傳統(tǒng)觀點(diǎn)，傳統(tǒng)觀點(diǎn)認(rèn)為aurora-A的過(guò)度活躍導(dǎo)致腫瘤,，包括一半以上的結(jié)腸癌,。但是Doe發(fā)現(xiàn)正常情況下，aurora-A和numb是腫瘤抑制物,，缺失aurora-A會(huì)加速新的成神經(jīng)細(xì)胞的過(guò)量表達(dá),，導(dǎo)致腫瘤。
部分英文原文：
Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation
Regulation of stem cell self-renewal versus differentiation is critical for embryonic development and adult tissue homeostasis. Drosophila larval neuroblasts divide asymmetrically to self-renew, and are a model system for studying stem cell self-renewal. Here we identify three mutations showing increased brain neuroblast numbers that map to the aurora-A gene, which encodes a conserved kinase implicated in human cancer. Clonal analysis and time-lapse imaging in aurora-A mutants show single neuroblasts generate multiple neuroblasts (ectopic self-renewal). This phenotype is due to two independent neuroblast defects: abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to align the mitotic spindle with the cortical polarity axis. numb mutant clones have ectopic neuroblasts, and Numb overexpression partially suppresses aurora-A neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that disrupt spindle alignment but not cortical polarity have increased neuroblasts. We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal.
