SphK1 confers resistance to apoptosis in gastric cancer cells by downregulating Bim via stimulating Akt/FoxO3a signaling

Xiong,Huaping; Wang,Jicheng; Guan,Hongyu; Wu,Jueheng; Xu,Ru; Wang,Min; Rong,Xia; Huang,Ke; Huang,Jieting; Liao,Qiao; Fu,Yongshui; Yuan,Jie

doi:10.3892/or.2014.3391

SphK1 confers resistance to apoptosis in gastric cancer cells by downregulating Bim via stimulating Akt/FoxO3a signaling

Authors:
- Huaping Xiong
- Jicheng Wang
- Hongyu Guan
- Jueheng Wu
- Ru Xu
- Min Wang
- Xia Rong
- Ke Huang
- Jieting Huang
- Qiao Liao
- Yongshui Fu
- Jie Yuan
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Affiliations: Guangzhou Blood Center, Institute of Blood Transfusion, Guangzhou, Guangdong 510095, P.R. China, Guangdong Women's and Children's Hospital, Medical Genetics Center, Guangzhou, Guangdong 510010, P.R. China, Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China, Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: August 7, 2014 https://doi.org/10.3892/or.2014.3391
Pages: 1369-1373
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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