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分子通路:肿瘤细胞篡夺大脑特异性代谢基因 CPT1C 以促进存活。

Molecular pathways: tumor cells Co-opt the brain-specific metabolism gene CPT1C to promote survival.

机构信息

Laboratory of Inflammation Biology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore.

出版信息

Clin Cancer Res. 2012 Nov 1;18(21):5850-5. doi: 10.1158/1078-0432.CCR-11-3281. Epub 2012 Sep 5.

Abstract

The metabolic adaptations of cancer cells are receiving renewed attention as potential targets for therapeutic exploitation. Recent work has highlighted the importance of fatty acid catabolism through β-oxidation to cellular energy homeostasis. In this article, we describe recent preclinical studies suggesting that a gene usually expressed only in the brain, carnitine palmitoyltransferase (CPT)1C, promotes cancer cell survival and tumor growth. CTP1C confers rapamycin resistance on breast cancer cells, indicating that this gene may act in a pathway parallel to mTOR-enhanced glycolysis. Because of CPT1C's normally brain-restricted expression and the inability of most drugs to pass the blood-brain barrier, CPT1C may be an ideal candidate for specific small-molecule inhibition. We further speculate that concurrent targeting of CPT1C activity and glycolysis in tumor cells could be a highly effective anticancer approach.

摘要

癌细胞的代谢适应正在重新引起人们的关注,因为它们可能成为治疗开发的潜在靶点。最近的研究强调了脂肪酸β-氧化分解为细胞能量稳态的重要性。在本文中,我们描述了最近的临床前研究表明,一种通常仅在大脑中表达的基因,肉碱棕榈酰转移酶(CPT)1C,促进了癌细胞的存活和肿瘤的生长。CPT1C 赋予乳腺癌细胞对雷帕霉素的抗性,表明该基因可能在与 mTOR 增强的糖酵解平行的途径中发挥作用。由于 CPT1C 的正常大脑限制表达和大多数药物无法通过血脑屏障,CPT1C 可能是特定小分子抑制的理想候选物。我们进一步推测,同时靶向肿瘤细胞中的 CPT1C 活性和糖酵解可能是一种非常有效的抗癌方法。

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