WWOX-mediated apoptosis in A549 cells mainly involves the mitochondrial pathway

Zhang, Ping; Jia, Renbing; Lei, Ying; Liu, Bo; Qian, Guofeng; Ge, Shengfang

doi:10.3892/mmr.2012.860

Cited by 16 publications

(6 citation statements)

References 12 publications

(18 reference statements)

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“…Such an effect of WWOX overexpression was found to be cosistant across various cell lines (17–24). While apoptosis seems to proceed through a mitochondrial pathway in breast, prostate and lung cells, Chiang et al showed that in U373MG glioblastoma cells, WWOX overexpression triggers a mitochondrial/caspase-3-independent pathway of apoptosis (25).…”

Section: Discussionmentioning

confidence: 99%

WWOX modulates the gene expression profile in the T98G glioblastoma cell line rendering its phenotype less malignant

Kośla¹,

Nowakowska²,

Pospiech³

2014

Oncology Reports

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The aim of the present study was to assess the influence of WWOX gene upregulation on the transcriptome and phenotype of the T98G glioblastoma cell line. The cells with high WWOX expression demonstrated a significantly different transcription profile for approximately 3,000 genes. The main cellular pathways affected were Wnt, TGFβ, Notch and Hedgehog. Moreover, the WWOX-transfected cells proliferated at less than half the rate, exhibited greatly lowered adhesion to ECM, increased apoptosis and impaired 3D culture formation. They also demonstrated an increased ability for crossing the basement membrane. Our results indicate that WWOX, apart from its tumor-suppressor function, appears to be a key regulator of the main cellular functions of the cell cycle and apoptosis. Furthermore, our results showed that WWOX may be involved in controlling metabolism, cytoskeletal structure and differentiation.

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Section: Discussionmentioning

confidence: 99%

WWOX modulates the gene expression profile in the T98G glioblastoma cell line rendering its phenotype less malignant

Kośla¹,

Nowakowska²,

Pospiech³

2014

Oncology Reports

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“…Apoptosis is a highly regulated, crucial biological process leading to cell death: Regulatory imbalance can cause excessive cell proliferation or apoptosis, leading to diseases including ovarian cancer. Several studies have demonstrated that abnormal apoptosis regulation in ovarian cells contributes to the development of ovarian cancer (2,3). Wild-type p53-induced phosphatase 1 [Wip1; official name: protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D)], a p53-dependent proto-oncogene first identified in 1997 (4), is widely involved in the regulation of multiple cell signaling pathways, and is important in the pathogenesis of cancers, including ovarian cancer (5–7).…”

Section: Introductionmentioning

confidence: 99%

Wip1 regulates SKOV3 cell apoptosis through the p38 MAPK signaling pathway

Feng¹,

Liu²,

Du³

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to explore the effect of silencing wild-type p53-induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase-3, caspase-3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl-2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated (p)-p38 MAPK. Reverse transcription-quantitative polymerase chain reaction was used to detect expression of p53, Bax, Bcl-2 and caspase-3 mRNAs. Compared with control, apoptosis of SKOV3 cell was significantly increased following Wip1 siRNA silencing. Wip1 silencing also resulted in a significant increase of p53 and p-p38 MAPK expression, as well as increased cleaved caspase-3/caspase-3 and Bax/Bcl-2 protein ratios. No significant differences were observed in apoptosis and apoptosis-related protein expression in the control siRNA transfected cells. The present study demonstrated that Wip1 silencing promotes apoptosis of human ovarian cancer SKOV3 cells by activation of the p38 MAPK signaling pathways and through subsequent upregulation of p53, and cleaved caspase-3/caspase-3 and Bax/Bcl-2 protein ratios. Overall, the findings of the present study suggest that targeting Wip1 may be a potential therapeutic avenue for the treatment of human ovarian cancer in the future.

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“…It should be noted here that consistent with results obtained with ezrin serine 66 phosphorylation mutants and its strongest ability to trigger PKA activation ( Fig 4B ), Fas ligand-induced cell death, contrary to TRAIL, was not significantly altered by pharmacological PKA regulators ( Fig 4C and S6 Fig ). PKA-induced phosphorylation of ezrin on S66 has been shown to regulate its interaction with WWOX ( WW domain-containing oxidoreductase) [ 26 ], a tumor suppressor protein [ 27 ] that regulates apoptosis induced at the mitochondrial level [ 28 ]. Interestingly, whereas both colon carcinoma cell lines SW480 and HCT116 express WWOX, two pancreatic cell lines, MIA PaCa-2 and PANC-1 as well as the SK-HEP-1 liver cancer cell line ( Fig 5A ) do not, and ectopic expression of ezrin wt in MIA PaCa-2 or SK-HEP-1 failed to regulate apoptosis induced by FasL or TRAIL ( Fig 5B ).…”

Section: Resultsmentioning

confidence: 99%

Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

et al. 2015

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Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type dependant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton- and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells.

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WWOX-mediated apoptosis in A549 cells mainly involves the mitochondrial pathway

Cited by 16 publications

References 12 publications

WWOX modulates the gene expression profile in the T98G glioblastoma cell line rendering its phenotype less malignant

WWOX modulates the gene expression profile in the T98G glioblastoma cell line rendering its phenotype less malignant

Wip1 regulates SKOV3 cell apoptosis through the p38 MAPK signaling pathway

Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

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