The fat side of prostate cancer.
The fat side of prostate cancer.
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DOI：
10.1016/j.bbalip.2013.03.010
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Loda M
中科院分区：
文献类型：
--
作者：
Zadra G;Photopoulos C;Loda M
与其他类型的实体癌相比，前列腺癌（PCa）的代谢似乎是独特的。正常前列腺细胞主要依靠葡萄糖氧化为柠檬酸的合成和分泌提供前体，导致克雷布斯循环不完整，能量产生的氧化磷酸化程度最低。相反，在转化过程中，PCa 细胞不再分泌柠檬酸盐，而是重新激活克雷布斯循环作为能量来源。此外，原发性 PCas 没有表现出有氧糖酵解增加，因此无法用 18F-FDG-PET 有效检测到它们。然而，脂质从头合成的增加与经典癌基因和抑癌基因的失调严格交织在一起，是该疾病的早期事件。脂肪生成酶（包括脂肪酸合酶和胆碱激酶）的上调和活性增加发生在前列腺癌的整个癌变过程中，并且与较差的预后和较差的生存率相关。因此，乙酸盐和胆碱等脂质前体已成功用作 PET 成像的替代示踪剂。脂质合成中间体和 FA 分解代谢也成为 PCa 维持的重要参与者。最后，流行病学研究表明，全身代谢紊乱（包括肥胖、代谢综合征和糖尿病）以及高热量和高脂肪饮食可能会增加患 PCa 的风险。然而，代谢紊乱如何促进前列腺癌的发展以及膳食脂质和肿瘤内合成的脂质是否代谢存在差异仍不清楚。在这篇综述中，我们研究了支持 PCa 发生和进展的脂质代谢的转变，并讨论了如何利用其脂肪生成性质进行治疗和诊断。
Prostate cancer (PCa) metabolism appears to be unique in comparison with other type of solid cancers. Normal prostate cells mainly rely on glucose oxidation to provide precursors for the synthesis and secretion of citrate, resulting in an incomplete Krebs cycle and minimal oxidative phosphorylation for energy production. In contrast, during transformation, PCa cells no longer secrete citrate and they reactivate the Krebs cycle as energy source. Moreover, primary PCas do not show increased aerobic glycolysis and therefore they are not efficiently detectable with 18F-FDG-PET. However, increased de novo lipid synthesis, strictly intertwined with deregulation in classical oncogenes and oncosuppressors, is an early event of the disease. Up-regulation and increased activity of lipogenic enzymes (including fatty acid synthase and choline kinase) occurs throughout PCa carcinogenesis and correlates with worse prognosis and poor survival. Thus, lipid precursors such as acetate and choline have been successfully used as alternative tracers for PET imaging. Lipid synthesis intermediates and FA catabolism also emerged as important players in PCa maintenance. Finally, epidemiologic studies suggested that systemic metabolic disorders including obesity, metabolic syndrome, and diabetes as well as hypercaloric and fat-rich diets might increase the risk of PCa. However, how metabolic disorders contribute to PCa development and whether dietary lipids and de novo lipids synthesized intra-tumor are differentially metabolized still remains unclear. In this review, we examine the switch in lipid metabolism supporting the development and progression of PCa and we discuss how we can exploit its lipogenic nature for therapeutic and diagnostic purposes.
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影响因子：
37.3
作者：
Costello, Leslie C;Franklin, Renty B
通讯作者：
Franklin, Renty B
影响因子：
4.7
作者：
Akinsete JA;Ion G;Witte TR;Hardman WE
通讯作者：
Hardman WE
影响因子：
28.2
作者：
Cantor JR;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
8
作者：
Buzzai, M;Bauer, DE;Thompson, CB
通讯作者：
Thompson, CB
DOI：
10.1111/j.1748-1716.1982.tb10600.x
发表时间：
1982-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
ARVER, S
通讯作者：
ARVER, S