SphK1 confers resistance to apoptosis in gastric cancer cells by downregulating Bim via stimulating Akt/FoxO3a signaling.
SphK1 confers resistance to apoptosis in gastric cancer cells by downregulating Bim via stimulating Akt/FoxO3a signaling.
复制标题
SphK1 通过刺激 Akt/FoxO3a 信号传导下调 Bim，赋予胃癌细胞抗凋亡能力
DOI：
10.3892/or.2014.3391
复制
发表时间：
2014-10
期刊：
影响因子：
4.2
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Xiong H;Wang J;Guan H;Wu J;Xu R;Wang M;Rong X;Huang K;Huang J;Liao Q;Fu Y;Yuan J
我们以前报道过鞘氨醇激酶1（SphK 1），一种催化鞘氨醇-1-磷酸（SIP）产生的酶，在人胃癌中上调，并预测不良的临床结果。在本研究中，我们使用已知的紫外线照射对人MGC-803胃癌细胞的差异效应，以确定其对SphK 1活性的影响。SphK 1在MGC-803胃癌细胞中的异位表达显著增强了其对紫外线照射的抵抗力，而用shRNA沉默内源SphK 1则削弱了这种能力。此外，这些抗凋亡作用与凋亡相关蛋白Bim的减少显著相关。我们进一步证明SphK 1可以通过诱导叉头框O3 a（FoxO 3a）的磷酸化来下调其转录活性，这被发现与PI 3 K/Akt信号通路有关。综上所述，我们的研究支持了SphK 1通过Akt/FoxO 3a/Bim途径赋予胃癌细胞凋亡抗性的理论。
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 antiapoptotic 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.
登录
查看更多内容
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
鞘氨醇激酶表达会增加细胞内鞘氨醇1-磷酸盐，并促进细胞生长和存活。
DOI：
10.1083/jcb.147.3.545
发表时间：
1999-11-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Olivera A;Kohama T;Edsall L;Nava V;Cuvillier O;Poulton S;Spiegel S
通讯作者：
Spiegel S
FOXO转录因子直接激活BIM基因表达并促进交感神经元中的凋亡。
影响因子：
7.8
作者：
Gilley, Jonathan;Coffer, Paul J;Ham, Jonathan
通讯作者：
Ham, Jonathan
影响因子：
4
作者：
Huang, Haojie;Tindall, Donald J.
通讯作者：
Tindall, Donald J.
影响因子：
4.7
作者：
Edsall, LC;Cuvillier, O;Milstien, S
通讯作者：
Milstien, S