title: MAGI2 enhances the sensitivity of BEL-7404 human hepatocellular carcinoma cells to staurosporine-induced apoptosis by increasing PTEN stability.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Zengxia
authors.initials: Z
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Jingjing
authors.initials: J
authors.lastname: Qi
authors.forename: Kun
authors.initials: K
authors.lastname: Fan
authors.forename: Peng
authors.initials: P
authors.lastname: Yin
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Yonglei
authors.initials: Y
authors.lastname: Liu
authors.forename: Wantong
authors.initials: W
authors.lastname: Yao
authors.forename: Xiumei
authors.initials: X
authors.lastname: Cai
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004789:Enzyme Activation; D004795:Enzyme Stability / Q000187:drug effects; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D051528:Guanylate Kinases; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D051057:Proto-Oncogene Proteins c-akt; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; D051059:PTEN Phosphohydrolase; D019311:Staurosporine