LRRC4 inhibits the proliferation of human glioma cells by modulating the expression of STMN1 and microtubule polymerization
LRRC4 inhibits the proliferation of human glioma cells by modulating the expression of STMN1 and microtubule polymerization
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LRRC4通过调节STMN1的表达和微管聚合抑制人胶质瘤细胞的增殖
DOI：
10.1002/jcb.23293
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发表时间：
2011-12
影响因子：
4
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Wang R;Wang Z;Yang J;Liu X;Wang L;Guo X;Zeng F;Wu M;Li G
LRRC4是一种胶质瘤的肿瘤抑制因子，在胶质瘤中普遍存在表观遗传失活。我们先前的研究表明，诱导LRRC4的表达抑制了胶质瘤细胞的增殖。然而，对LRRC4在胶质瘤细胞中的作用机制知之甚少。我们利用二维荧光差示凝胶电泳法(2-D DGE)和MALDI-TOF/TOF-MS/MS鉴定了11个差异表达的蛋白质，其中包括表达LRRC4的U251胶质瘤细胞中显著下调的STMN1表达。STMN1的表达水平与人脑胶质瘤的病理程度呈正相关。此外，诱导LRRC4过表达在体外抑制了STMN1的表达和U251细胞的增殖，并在体内抑制了胶质瘤的生长。此外，诱导LRRC4或下调STMN1的表达可诱导U251细胞周期停滞，其机制可能与调节U251细胞中p21、细胞周期蛋白D1和细胞周期蛋白B的表达，调节ERK的磷酸化，抑制CDK5和cdc2的活性，但增加微管蛋白聚合有关。LRRC4至少部分通过下调STMN1的表达，作为主要的胶质瘤抑制因子，诱导细胞周期停滞，调节微管蛋白的动态过程，从而抑制胶质瘤细胞的增殖和生长。潜在地，LRRC4或STMN1表达的调节可能有助于设计干预胶质瘤的新疗法。J.细胞。生物化学。112：3621-3629,2011。©2011 Wiley期刊，Inc.
LRRC4 is a tumor suppressor of glioma, and it is epigenetically inactivated commonly in glioma. Our previous study has shown that induction of LRRC4 expression inhibits the proliferation of glioma cells. However, little is known about the mechanisms underlying the action of LRRC4 in glioma cells. We employed two‐dimensional fluorescence differential gel electrophoresis (2‐D DIGE) and MALDI –TOF/TOF‐MS/MS to identify 11 differentially expressed proteins, including the significantly down‐regulated STMN1 expression in the LRRC4‐expressing U251 glioma cells. The levels of STMN1 expression appeared to be positively associated with the pathogenic degrees of human glioma. Furthermore, induction of LRRC4 over‐expression inhibited the STMN1 expression and U251 cell proliferation in vitro, and the glioma growth in vivo. In addition, induction of LRRC4 or knockdown of STMN1 expression induced cell cycle arrest in U251 cells, which was associated with modulating the p21, cyclin D1, and cyclin B expression, and the ERK phosphorylation, and inhibiting the CDK5 and cdc2 kinase activities, but increasing the microtubulin polymerization in U251 cells. LRRC4, at least partially by down‐regulating the STMN1expression, acts as a major glioma suppressor, induces cell cycle arrest and modulates the dynamic process of microtubulin, leading to the inhibition of glioma cell proliferation and growth. Potentially, modulation of LRRC4 or STMN1 expression may be useful for design of new therapies for the intervention of glioma. J. Cell. Biochem. 112: 3621–3629, 2011. © 2011 Wiley Periodicals, Inc.
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影响因子：
3.7
作者：
Qiu-hong Zhang;Ming‐hua Wu;Li-li Wang;Li Cao;Ke Tang;C. Peng;Kai Gan;Xiao-Ling Li;Gui-yuan Li-Gui
通讯作者：
Qiu-hong Zhang;Ming‐hua Wu;Li-li Wang;Li Cao;Ke Tang;C. Peng;Kai Gan;Xiao-Ling Li;Gui-yuan Li-Gui
DOI：
--
发表时间：
2009-09
期刊：
Journal of biomolecular techniques : JBT
影响因子：
--
作者：
M. Cilia;T. Fish;X. Yang;M. Mclaughlin;T. Thannhauser;S. Gray
通讯作者：
M. Cilia;T. Fish;X. Yang;M. Mclaughlin;T. Thannhauser;S. Gray
LRRC4 通过下调多效细胞因子表达和反应来抑制胶质母细胞瘤细胞增殖、迁移和血管生成
影响因子：
5.6
作者：
Wu, Minghua;Huang, Chen;Li, Guiyuan
通讯作者：
Li, Guiyuan
影响因子：
3.3
作者：
Wu, Minghua;Huang, Chen;Li, Guiyuan
通讯作者：
Li, Guiyuan
DOI：
--
发表时间：
2002-10
期刊：
The Mount Sinai journal of medicine, New York
影响因子：
--
作者：
S. Mistry;G. Atweh
通讯作者：
S. Mistry;G. Atweh