title: SphK1 confers resistance to apoptosis in gastric cancer cells by downregulating Bim via stimulating Akt/FoxO3a signaling.
abstract: We previously reported that sphingosine kinase 1 (SphK1), an enzyme that catalyzes the production of sphingosine-1-phosphate (SIP), is upregulated in human gastric cancer and predicts poor clinical outcome. In the present study, we used known differential effects of UV irradiation on human MGC-803 gastric cancer cells to determine their effect on SphK1 activity. Ectopic expression of SphK1 in MGC-803 gastric cancer cells markedly enhanced their resistance to UV irradiation, whereas silencing endogenous SphK1 with shRNAs weakened this ability. Furthermore, these anti-apoptotic effects were significantly associated with decrease of Bim, an apoptosis-related protein. We further demonstrated that SphK1 could downregulate the transcriptional activity of forkhead box O3a (FoxO3a) by inducing its phosphorylation, which was found to be associated with the PI3K/Akt signaling. Taken together, our study supports the theory that SphK1 confers resistance to apoptosis in gastric cancer cells via the Akt/FoxO3a/Bim pathway.
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Guangdong Women's and Children's Hospital, Medical Genetics Center, Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Ru
authors.initials: R
authors.lastname: Xu
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Rong
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Jieting
authors.initials: J
authors.lastname: Huang
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Yongshui
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation; D000099157:Sphingosine Kinase
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008246:Lysophospholipids; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D013110:Sphingosine; D000099157:Sphingosine Kinase; C000606775:BCL2L11 protein, human; C499517:FOXO3 protein, human; C060506:sphingosine 1-phosphate
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