PNAS上的5月份的一篇文章

fananran2003

c-Met signaling induces a reprogramming network and supports the glioblastoma stem-like phenotype.  ]2 p: L/ M5 M+ t, Y
Li Y, Li A, Glas M, Lal B, Ying M, Sang Y, Xia S, Trageser D, Guerrero-Cázares H, Eberhart CG, Quiñones-Hinojosa A, Scheffler B, Laterra J.  i! ]8 M' q3 H2 Q: N
SourceHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205.
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The tyrosine kinase c-Met promotes the formation and malignant progression of multiple cancers. It is well known that c-Met hyperactivation increases tumorigenicity and tumor cell resistance to DNA damaging agents, properties associated with tumor-initiating stem cells. However, a link between c-Met signaling and the formation and/or maintenance of neoplastic stem cells has not been previously identified. Here, we show that c-Met is activated and functional in glioblastoma (GBM) neurospheres enriched for glioblastoma tumor-initiating stem cells and that c-Met expression/function correlates with stem cell marker expression and the neoplastic stem cell phenotype in glioblastoma neurospheres and clinical glioblastoma specimens. c-Met activation was found to induce the expression of reprogramming transcription factors (RFs) known to support embryonic stem cells and induce differentiated cells to form pluripotent stem (iPS) cells, and c-Met activation counteracted the effects of forced differentiation in glioblastoma neurospheres. Expression of the reprogramming transcription factor Nanog by glioblastoma cells is shown to mediate the ability of c-Met to induce the stem cell characteristics of neurosphere formation and neurosphere cell self-renewal. These findings show that c-Met enhances the population of glioblastoma stem cells (GBM SCs) via a mechanism requiring Nanog and potentially other c-Met-responsive reprogramming transcription factors.
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c-Met 信号诱导一种重编程网络并支持与成胶质细胞瘤干性相似的表型
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  酪氨酸激酶c-Met促进多种癌症的形成于恶性增殖。众所周知，c-Met的过度活性增加肿瘤的发生以及肿瘤细胞对NDA 损伤剂的抗性，及其与肿瘤形成干细胞相关的特性。但是，c-Met信号与肿瘤干细胞的形成和（或）维持之间的联系至今仍未确定。本文中发现：c-Met 在成胶质细胞瘤肿瘤干细胞富集的成胶质细胞瘤神经球被激活并发挥作用，c-Met 的表达/功能与干细胞标记的表达以及肿瘤干细胞在成胶质细胞瘤神经球和临床成胶质细胞瘤样本的表型有关。发现c-Met 激活能诱导支持胚胎干细胞和诱导分化细胞形成iPS的重编程转录因子（RF）的表达。转录因子Nanog 在成胶质细胞瘤中的表达被发现能介导c-Met 诱导神经球形成以及神经球细胞自我更新的干细胞特性的能力。这些表明，c-Met 能通过一种需要Nanog或者其他潜在的c-Met 相关重编程转录因子的机制提升成胶质细胞瘤干细胞的数目。: |  \& B2 y# A* \$ k4 B
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pinger

很好，高手