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SLC22A5(OCTN2)肉碱转运体——细胞代谢不可或缺的“双面人”,也是人类癌症的“两面派”。

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

机构信息

Laboratory of Transport through Biomembranes, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.

出版信息

Molecules. 2019 Dec 19;25(1):14. doi: 10.3390/molecules25010014.

Abstract

Oxidation of fatty acids uses l-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.

摘要

脂肪酸的氧化利用左旋肉碱将酰基部分转运到线粒体中,这一过程被称为肉碱穿梭。β-氧化过程也发生在癌细胞中。大部分肉碱来自饮食,通过广泛表达的有机阳离子转运体新型家族成员 2(OCTN2)/溶质载体家族 22 成员 5(SLC22A5)转运到细胞内。的表达受转录因子过氧化物酶体增殖物激活受体(PPARs)和雌激素受体调节。通过 OCTN2 与其他蛋白质(如 PDZ 结构域蛋白、蛋白磷酸酶 PP2A、窖蛋白-1、蛋白激酶 C)的相互作用,可控制转运体向细胞表面的输送和转运活性。在许多类型的癌症中,的表达发生改变,通过为β-氧化提供肉碱,为一些癌症细胞提供了生长和增殖的替代葡萄糖能源优势。另一方面,SLC22A5 还可以转运临床上使用的几种化疗药物,导致癌细胞死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb01/6982704/74c4bd8502d3/molecules-25-00014-g001.jpg

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