TNFAIP8 drives metabolic reprogramming to promote prostate cancer cell proliferation.
TNFAIP8 drives metabolic reprogramming to promote prostate cancer cell proliferation.
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DOI：
10.1016/j.biocel.2020.105885
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Kumar D
中科院分区：
文献类型：
--
作者：
Niture S;Lin M;Odera JO;Moore J;Zhe H;Chen X;Suy S;Collins SP;Kumar D
肿瘤坏死因子-α-诱导蛋白8（TNFAIP 8）是TIPE/TNFAIP 8家族成员之一，参与多种肿瘤的发生和发展。我们假设TNFAIP 8通过调节氧化磷酸化（OXPHOS）和糖酵解促进前列腺癌（PCa）进展。TNFAIP 8的异位表达通过增强细胞代谢活性而增加PCa细胞增殖/迁移/球体形成。在机制上，TNFAIP 8激活PI 3 K-AKT通路并上调PCa细胞存活。还发现TNFAIP 8调节葡萄糖代谢酶的表达，增强葡萄糖消耗和内源性ATP产生。用糖酵解抑制剂2-脱氧葡萄糖（2-DG）处理减少TNFAIP 8介导的葡萄糖消耗、ATP产生、球状体形成和PCa细胞迁移。通过维持线粒体膜电位，TNFAIP 8增加OXPHOS和糖酵解。此外，TNFAIP 8调节PCa细胞中糖酵解代谢物的产生。总的来说，我们的数据表明TNFAIP 8通过增强葡萄糖代谢和促进PCa细胞中的代谢重编程来发挥其致癌作用。因此，TNFAIP 8可能是与前列腺癌相关的生物标志物，并指示潜在的治疗靶点。
Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of TIPE/TNFAIP8 family, has been involved in the development and progression of various human cancers. We hypothesized that TNFAIP8 promotes prostate cancer (PCa) progression via regulation of oxidative phosphorylation (OXPHOS) and glycolysis. Ectopic expression of TNFAIP8 increased PCa cell proliferation/migration/spheroid formation by enhancing cell metabolic activities. Mechanistically, TNFAIP8 activated the PI3K-AKT pathway and up-regulated PCa cell survival. TNFAIP8 was also found to regulate the expression of glucose metabolizing enzymes, enhancing glucose consumption, and endogenous ATP production. Treatment with a glycolysis inhibitor, 2-deoxyglucose (2-DG), reduced TNFAIP8 mediated glucose consumption, ATP production, spheroid formation, and PCa cell migration. By maintaining mitochondrial membrane potential, TNFAIP8 increased OXPHOS and glycolysis. Moreover, TNFAIP8 modulates the production of glycolytic metabolites in PCa cells. Collectively, our data suggest that TNFAIP8 exerts its oncogenic effects by enhancing glucose metabolism and by facilitating metabolic reprogramming in PCa cells. Therefore, TNFAIP8 may be a biomarker associated with prostate cancer and indicate a potential therapeutic target.
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