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RhoA regulates invasion of glioma cells via the c-Jun NH2-terminal kinase pathway under hypoxia

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单位: [1]Huazhong Univ Sci & Technol,Dept Neurosurg,Tongji Hosp,Tongji Med Coll,Wuhan 430030,Hubei,Peoples R China
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关键词: glioma cell invasion hypoxia U251 cell line RhoA-JNK signaling pathway matrix metalloproteinase-2

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The purpose of this study was to investigate the mechanism of glioma cell invasion in hypoxic conditions. We demonstrated that hypoxia increased cell invasion, matrix metalloproteinase-2 (MMP2) activity and time-dependent expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) in human glioma cells. These data suggest that MMP2 may play a significant role in tumor invasion in hypoxic conditions. We investigated the mechanisms involved in the increased MMP2 activity and cell invasion in hypoxic conditions. Increased expression of phospho-Jun NH2-terminal kinase (p-JNK) and phospho-c-Jun (p-c-Jun) in glioma cells induced by hypoxia was detected. Furthermore, this effect may be reduced by inhibiting the JNK signaling pathway. We found that inhibition of RhoA geranylgeranylation by geranylgeranyltransferase inhibitor-2147 (GGTI-2147) or knockdown of RhoA by si RNA against RhoA reduced the expression of p-JNK and p-c-Jun, and decreased MMP2 activity and glioma cell invasion in hypoxic conditions. These data suggest a link among RhoA, JNK, c-Jun and MMP2 activity that is functionally involved in the increased glioma cell invasion induced by hypoxia.

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出版当年[2011]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2010]版:
Q4 ONCOLOGY
最新[2023]版:
Q3 ONCOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol,Dept Neurosurg,Tongji Hosp,Tongji Med Coll,Wuhan 430030,Hubei,Peoples R China
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