GOLPH3 may act as a scaffold protein to regulate JAK2-STAT3 interaction and then its activation, which therefore mediates the effect of GOLPH3 on cell proliferation.
Background: Abnormally expressed the p21-activated kinases (PAKs) are implicated in the development and treatment of glioma. Previous study has reported that PAK1 is expressed in glioma. However, the role and mechanism of PAK1 in glioma progression remain unclear.Methods: Western blotting was employed to detect the expression of PAK1 in human glioma tissues. CCK-8, EdU and colony formation assay were applied to evaluate the effect of PAK1 inhibition on cell proliferation of glioma. The flow cytometry was utilized to examine the cell cycle distribution and apoptotic rate of glioma. Wound healing and transwell assay were exploited to investigate the effect of PAK1 inhibition on cell migration and invasion of glioma. The orthotopic xenograft glioma model was established to probe the effect of PAK1 silencing on tumor formation of U87 cell. Results: It was showed that PAK1 was significantly upregulated in glioma tissues. Besides, high level of PAK1 was found to be associated with poor prognosis in glioma patients in TCGA database. PAK1 inhibition restrained cell proliferation, arrested cells at G1 phase, and induced cell apoptosis of glioma. PAK1 inhibition suppressed glioma cell migration and invasion. Moreover, knockdown of PAK1 dramatically decreased the protein expressions including MDM2, p38, p-p38, CyclinD1, CDK4, Bcl-2, MMP2, MMP9, Cofilin, while increased the protein levels of p53, Bax, p21 and Cleaved Caspase-3. Finally, orthotopic xenograft glioma model confirmed that silencing of PAK1 repressed the tumor formation of U87 cell transplantation.Conclusion: Our study described that PAK1 inhibition impedes proliferation, migration and invasion of glioma cells and thus probably as a novel target for glioma therapy.
aims: This study aims to explore the roles and mechanisms of PAK1 in glioma. background: p21-activated kinase 1 (PAK1) is abnormally expressed in glioma; however, its roles and mechanisms in glioma remain unclear. objective: To explore the effects of PAK1 inhibition on the proliferation, migration and invasion of glioma cells. method: Cell Counting Kit-8 (CCK-8), 5‐ethynyl‐20‐deoxyuridine (EdU) incorporation and colony formation assays were performed to evaluate the effects of PAK1 inhibition on the proliferation of glioma cells. Flow cytometry was used to examine the cell cycle distribution and apoptosis rate of the glioma cells. Wound healing and Transwell assays were performed to investigate the effects of PAK1 inhibition on glioma cell migration and invasion. The orthotopic xenograft glioma model was used to probe the effect of PAK1 silencing on glioma tumor formation. result: PAK1 inhibition arrested cells at the G1 phase, and induced apoptosis of glioma cells. Moreover, knockdown of PAK1 decreased the protein expression levels of MDM2, p38, p-p38, CyclinD1, CDK4, Bcl-2, MMP2, MMP9 and cofilin, but increased the protein levels of p53, Bax, p21 and cleaved caspase-3. Finally, a xenograft glioma model confirmed that silencing of PAK1 repressed U87 cell transplantation tumor formation. conclusion: This study showed that PAK1 inhibition impedes the proliferation, migration and invasion of glioma cells. other: PAK1 may serve as a novel target for glioma therapy.
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