日本科学家发现，一个特定基因可以使癌干细胞变成普通癌细胞，从而阻止一种恶性脑癌——成胶质细胞瘤复发。
成胶质细胞瘤是脑癌中常见的一种，经常导致患者在短时间内死亡，手术切除肿瘤组织后容易复发。此前研究发现，癌干细胞是癌症复发和转移的原因之一，这类细胞与普通癌细胞不同，能够不断自我复制，并能分化成多种癌细胞。
日本山形国立大学和国立癌症研究中心的研究小组报告说，他们对成胶质细胞瘤的普通癌细胞和癌干细胞的基因进行了比较分析，结果发现一个称为FoxO3a的基因在普通癌细胞中发挥作用，而在癌干细胞中处于沉睡状态。
动物实验表明，如果激活癌干细胞中的FoxO3a基因，癌干细胞就变成了没有增殖能力的普通癌细胞，不会再无限分裂。
研究论文发表在新一期美国《干细胞》杂志网络版上。研究小组已经找到了可以让该基因发挥作用的物质，正准备以此为基础开发药物。（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
