MAGI2 enhances the sensitivity of BEL-7404 human hepatocellular carcinoma cells to staurosporine-induced apoptosis by increasing PTEN stability

Li,Xin; Li,Zengxia; Li,Na; Qi,Jingjing; Fan,Kun; Yin,Peng; Zhao,Chao; Liu,Yonglei; Yao,Wantong; Cai,Xiumei; Wang,Liying; Zha,Xiliang

doi:10.3892/ijmm.2013.1411

MAGI2 enhances the sensitivity of BEL-7404 human hepatocellular carcinoma cells to staurosporine-induced apoptosis by increasing PTEN stability

Authors:
- Xin Li
- Zengxia Li
- Na Li
- Jingjing Qi
- Kun Fan
- Peng Yin
- Chao Zhao
- Yonglei Liu
- Wantong Yao
- Xiumei Cai
- Liying Wang
- Xiliang Zha
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, P.R. China, Key Laboratory of Glycoconjugate Research, Ministry of Health, Shanghai 200032, P.R. China, Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai 200032, P.R. China
Published online on: June 7, 2013 https://doi.org/10.3892/ijmm.2013.1411
Pages: 439-447

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Abstract

Adaptor proteins are involved in the assembly of various intracellular complexes and the regulation of cellular functions. Membrane-associated guanylate kinase inverted 2 (MAGI2), also known as synaptic scaffolding molecule (S-SCAM), plays a critical role in signal transduction by assembling and anchoring its ligands. However, the role of MAGI2 in mediating apoptosis remains largely unknown. In the present study, BEL-7404 human hepatocellular carcinoma cells were transfected with a plasmid containing myc-MAGI2 or an empty plasmid and cell viability was then determined using the Cell Counting kit-8. Apoptosis was also detected using an Annexin V apoptosis assay. The cells were then treated with various doses of staurosporine (STS) for different periods of time. The overexpression of myc-MAGI2 was found to sensitize the BEL-7404 cells to apoptosis in response to STS in a time- and dose-dependent manner. Our results demonstrated that MAGI2 enhanced STS-induced apoptosis by increasing the protein expression of cytoplasmic phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and decreasing its protein degradation. The apoptotic sensitivity of the cells caused by the overexpression of myc-MAGI2 was reversed by the silencing of PTEN expression by PTEN siRNA, thus revealing a momentous role of PTEN in the enhancement of the sensitivity of cancer cells to STS-induced apoptosis by MAGI2. Finally, we observed that the MAGI-PTEN complex triggered by MAGI2 overexpression reduced the phosphorylation levels of AKT. These results suggest that MAGI2 overexpression enhances the sensitivity of cancer cells harboring ectopic PTEN to STS-induced apoptosis.

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