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

Tong,Jiao  Jian; Yan,Zhang; Jian,Ren; Tao,Huang; Hui,Ouyang  Tao; Jian,Chen

doi:10.3892/ol.2012.777

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

Authors:
- Jiao Jian Tong
- Zhang Yan
- Ren Jian
- Huang Tao
- Ouyang Tao Hui
- Chen Jian
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Affiliations: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: June 27, 2012 https://doi.org/10.3892/ol.2012.777
Pages: 495-500

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Abstract

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-1α (HIF‑1α) 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 siRNA 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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