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SLC22A5 (OCTN2) Carnitine Transporter—Indispensable for Cell Metabolism a Jekyll and Hyde of Human Cancer

机译:SLC22A5(OCTN2)肉碱转运蛋白-细胞代谢必不可少的人类癌症的吉柯和海德

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摘要

Oxidation of fatty acids uses -carnitine to transport acyl moieties to mitochondria in a so-called carnitine shuttle. The process of β-oxidation also takes place in cancer cells. The majority of carnitine comes from the diet and is transported to the cell by ubiquitously expressed organic cation transporter novel family member 2 (OCTN2)/solute carrier family 22 member 5 (SLC22A5). The expression of is regulated by transcription factors peroxisome proliferator-activated receptors (PPARs) and estrogen receptor. Transporter delivery to the cell surface, as well as transport activity are controlled by OCTN2 interaction with other proteins, such as PDZ-domain containing proteins, protein phosphatase PP2A, caveolin-1, protein kinase C. expression is altered in many types of cancer, giving an advantage to some of them by supplying carnitine for β-oxidation, thus providing an alternative to glucose source of energy for growth and proliferation. On the other hand, SLC22A5 can also transport several chemotherapeutics used in clinics, leading to cancer cell death.
机译:脂肪酸的氧化使用-肉碱将酰基部分以所谓的“肉碱”穿梭转运至线粒体。 β-氧化过程也发生在癌细胞中。肉碱的大部分来自饮食,并通过普遍表达的有机阳离子转运蛋白新家族成员2(OCTN2)/溶质载体家族22成员5(SLC22A5)转运至细胞。的表达受转录因子过氧化物酶体增殖物激活受体(PPAR)和雌激素受体的调节。 OCTN2与其他蛋白质(例如含PDZ域的蛋白质,蛋白质磷酸酶PP2A,caveolin-1和蛋白质激酶C)的相互作用控制着转运蛋白向细胞表面的转运以及转运活性。在许多类型的癌症中,表达都发生了改变,通过提供肉碱以进行β氧化,从而为其中一些提供了优势,从而为葡萄糖的生长和增殖提供了替代能源。另一方面,SLC22A5也可以运输临床中使用的几种化学疗法,导致癌细胞死亡。

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