日本科學(xué)家發(fā)現(xiàn)，一個特定基因可以使癌干細(xì)胞變成普通癌細(xì)胞，從而阻止一種惡性腦癌——成膠質(zhì)細(xì)胞瘤復(fù)發(fā),。
成膠質(zhì)細(xì)胞瘤是腦癌中常見的一種，經(jīng)常導(dǎo)致患者在短時間內(nèi)死亡，手術(shù)切除腫瘤組織后容易復(fù)發(fā),。此前研究發(fā)現(xiàn)，癌干細(xì)胞是癌癥復(fù)發(fā)和轉(zhuǎn)移的原因之一,，這類細(xì)胞與普通癌細(xì)胞不同,，能夠不斷自我復(fù)制，并能分化成多種癌細(xì)胞。
日本山形國立大學(xué)和國立癌癥研究中心的研究小組報告說,，他們對成膠質(zhì)細(xì)胞瘤的普通癌細(xì)胞和癌干細(xì)胞的基因進(jìn)行了比較分析,，結(jié)果發(fā)現(xiàn)一個稱為FoxO3a的基因在普通癌細(xì)胞中發(fā)揮作用，而在癌干細(xì)胞中處于沉睡狀態(tài),。
動物實驗表明,，如果激活癌干細(xì)胞中的FoxO3a基因，癌干細(xì)胞就變成了沒有增殖能力的普通癌細(xì)胞,，不會再無限分裂,。
研究論文發(fā)表在新一期美國《干細(xì)胞》雜志網(wǎng)絡(luò)版上。研究小組已經(jīng)找到了可以讓該基因發(fā)揮作用的物質(zhì),，正準(zhǔn)備以此為基礎(chǔ)開發(fā)藥物,。（生物谷 Bioon.com）
doi:10.1002/stem.696
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FoxO3a Functions as a Key Integrator of Cellular Signals That Control Glioblastoma Stem‐like Cell Differentiation and Tumorigenicity
Sunayama, Jun; Sato, Atsushi; Matsuda, Ken‐Ichiro; Tachibana, Ken; Watanabe, Eriko; Seino, Shizuka; Suzuki, Kaori; Narita, Yoshitaka; Shibui, Soichiro; Sakurada, Kaori; Kayama, Takamasa; Tomiyama, Arata; Kitanaka, Chifumi
Keywords:FoxO3a;Akt;Extracellular signal‐\regulated kinase;p70S6K;Glioblastoma stem cellsAbstractGlioblastoma is one of the most aggressive types of human cancer, with invariable and fatal recurrence even after multimodal intervention, for which cancer stem‐like cells (CSLCs) are now being held responsible. Our recent findings indicated that combinational inhibition of phosphoinositide‐3‐kinase/Akt/mammalian target of rapamycin (mTOR) and mitogen‐activated protein/extracellular signal‐\regulated kinase kinase (MEK)/extracellular signal‐\regulated kinase (ERK) pathways effectively promotes the commitment of glioblastoma CSLCs to differentiation and thereby suppresses their tumorigenicity. However, the mechanism by which these two signaling pathways are coordinated to regulate differentiation and tumorigenicity remains unknown. Here, we identified FoxO3a, a common phosphorylation target for Akt and ERK, as a key transcription factor that integrates the signals from these pathways. Combinational blockade of both the pathways caused nuclear accumulation and activation of FoxO3a more efficiently than blockade of either alone, and promoted differentiation of glioblastoma CSLCs in a FoxO3a expression‐dependent manner. Furthermore, the expression of a constitutively active FoxO3a mutant lacking phosphorylation sites for both Akt and ERK was sufficient to induce differentiation and reduce tumorigenicity of glioblastoma CSLCs. These findings suggest that FoxO3a may play a pivotal role in the control of differentiation and tumorigenicity of glioblastoma CSLCs by the PI3K/Akt/mTOR and MEK/ERK signaling pathways, and also imply that developing methods targeting effective FoxO3a activation could be a potential approach to the treatment of glioblastoma. STEM CELLS 2011;29:1327–1337
