title: RhoA regulates invasion of glioma cells via the c-Jun NH2-terminal kinase pathway under hypoxia.
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.
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Jiao Jian
authors.initials: JJ
authors.lastname: Tong
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yan
authors.forename: Ren
authors.initials: R
authors.lastname: Jian
authors.forename: Huang
authors.initials: H
authors.lastname: Tao
authors.forename: Ouyang Tao
authors.initials: OT
authors.lastname: Hui
authors.forename: Chen
authors.initials: C
authors.lastname: Jian
keywords: RhoA-JNK signaling pathway; U251 cell line; cell invasion; glioma; hypoxia; matrix metalloproteinase-2