Loss of SH3GL2 promotes the migration and invasion behaviours of glioblastoma cells through activating the STAT3/MMP2 signalling

Zhu, Y.; Zhang, Xiang; Wang, Lei; Ji, Zhe; Xie, Manyi; Zhou, Xinyu; Liu, Zhiyi; Shi, Hengliang; Yu, Rutong

doi:10.1111/jcmm.13184

Cited by 25 publications

(22 citation statements)

References 38 publications

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“…This feature enables them to enhance stemness and aberrant cell survival, leading to tumorigenesis [ 38 , 39 ]. The Src-linked STAT3/MMP pathway is known to be required for GSC maintenance, partially through upregulating the expression of Toll-like receptor 9 (TLR9) [ 40 , 41 ]. Stimulation of TLR9 with a CpG ligand (CpG oligodeoxynucleotide) activated STAT3 pathway signaling and promoted GSC growth, whereas silencing TLR9 expression abrogated GSC development [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Src is the primary target of aripiprazole, an atypical antipsychotic drug, in its anti-tumor action

et al. 2017

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Aripiprazole (ARP) is an atypical anti-psychotic drug widely used to treat schizophrenia and bipolar disorder. The pharmacological effects of ARP on cancer cells are still poorly understood. In this study, anti-cancer effects of ARP on various malignant tumor cells and its molecular mechanism were further carefully examined by using cell proliferation assay, xenograft mouse model, immunoblotting analysis, migration assay, luciferase reporter gene assay, kinase assay, and overexpression strategy. Treatment with ARP induced cytotoxicity in U251 glioma cells, MKN-1 gastric adenosquamous carcinoma cells, and CT26 colon carcinoma cells. ARP suppressed cell proliferation of LN428, MDA-MB-231, and HEK293 cells. Pro-apoptotic factors active caspase-3, -8, and -9, as well as p53, were upregulated, whereas the protein and mRNA levels of anti-apoptotic factor B-cell lymphoma 2 (Bcl-2) decreased. In agreement with the in vitro results, ARP compound also significantly suppressed the growth of tumor masses formed by injecting CT26 colon cancer cells into mice. ARP treatment also effectively decreased the migratory ability of U251 glioma cells by downregulating metalloproteinase-9. Levels of phosphorylated Src, phosphorylated phosphatidylinositide 3-kinase (PI3K), and phosphorylated signal transducer and activator of transcription 3 (STAT3) were significantly decreased following ARP treatment. ARP compound reduced the kinase activity of Src. Our studies suggest that Src may be an important target molecule linked to the antitumor effects of ARP.

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Section: Discussionmentioning

confidence: 99%

Src is the primary target of aripiprazole, an atypical antipsychotic drug, in its anti-tumor action

et al. 2017

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“…The stable cell lines were developed as we previously described. [22][23][24] For stably knocking down or overexpressing PHAP1, the U251 and U87 cells were infected with the control, shPHAP1#3, GFP or GFP-PHAP1 lentiviruses, respectively. Forty-eight hours after infection, the cells were continuously provided with the medium supplemented with 2.5 lg/mL puromycin (Sigma, St. Louis, MO, USA).…”

Section: Development Of the Stable Cell Linesmentioning

confidence: 99%

PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway

Xie

Bao

et al. 2018

J Cellular Molecular Medi

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PHAP1 (Putative HLA‐DR‐associated protein 1), also termed acidic leucine‐rich nuclear phosphoprotein 32A (ANP32A), Phosphoprotein 32 (pp32) or protein phosphatase 2A inhibitor (I1PP2A), is a multifunctional protein aberrantly expressed in multiple types of human cancers. However, its expression pattern and clinical relevance in human glioma remain unknown. In this study, Western blotting and immunohistochemistry analysis demonstrated PHAP1 protein was highly expressed in glioma patients, especially in those with high‐grade disease. Publicly available data also revealed high levels of PHAP1 were associated with poor prognosis in glioma patients. The functional studies showed that knock‐down of PHAP1 suppressed the proliferation of glioma cells, while overexpression of PHAP1 facilitated it. The iTRAQ proteomic analysis suggested that stathmin might be a potential downstream target of PHAP1. Consistently, PHAP1 knock‐down significantly decreased the expression of stathmin, while overexpression of PHAP1 increased it. Also, the upstream negative regulator, p27, expression levels increased upon PHAP1 knock‐down and decreased when PHAP1 was overexpressed. As a result, the phosphorylated Akt (S473), an upstream regulator of p27, expression levels decreased upon silencing of PHAP1, but elevated after PHAP1 overexpression. Importantly, we demonstrate the p27 down‐regulation, stathmin up‐regulation and cell proliferation acceleration induced by PHAP1 overexpression were dependent on Akt activation. In conclusion, the above results suggest that PHAP1 expression is elevated in glioma patients, which may accelerate the proliferation of glioma cells by regulating the Akt/p27/stathmin pathway.

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“…Malignant glioma is the most common type of primary intracranial tumors in adults, and accounts for about 70 percent of human brain tumors [25]. Specially, characterized by its high heterogeneous, widespread consistent infiltration, quick malignant progression.…”

Section: Discussionmentioning

confidence: 99%

Effect of p21-activated kinase 1 inhibition on proliferation, migration and invasion of glioma

Yi¹,

Chen²,

Zhou³

et al. 2020

Preprint

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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.

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Loss of SH3GL2 promotes the migration and invasion behaviours of glioblastoma cells through activating the STAT3/MMP2 signalling

Cited by 25 publications

References 38 publications

Src is the primary target of aripiprazole, an atypical antipsychotic drug, in its anti-tumor action

Src is the primary target of aripiprazole, an atypical antipsychotic drug, in its anti-tumor action

PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway

Effect of p21-activated kinase 1 inhibition on proliferation, migration and invasion of glioma

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