SLC transporters as a novel class of tumour suppressors: identity, function and molecular mechanisms.
SLC transporters as a novel class of tumour suppressors: identity, function and molecular mechanisms.
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DOI：
10.1042/bj20150751
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发表时间：
2016-05-01
期刊：
影响因子：
--
通讯作者：
Ganapathy V
中科院分区：
文献类型：
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作者：
Bhutia YD;Babu E;Ramachandran S;Yang S;Thangaraju M;Ganapathy V
近年来，质膜转运蛋白在肿瘤中的作用越来越受到关注。几种必需营养素的转运蛋白在癌症中上调，并作为肿瘤促进剂。转运蛋白也可以作为肿瘤抑制剂。迄今为止，四个转运蛋白属于SLC基因家族已被确定为肿瘤抑制因子。SLC 5A 8是一种Na+偶联的单羧酸转运蛋白。其底物包括细菌发酵产物丁酸盐和丙酸盐以及普遍存在的代谢产物丙酮酸盐。该转运蛋白的肿瘤抑制功能与丁酸盐、丙酸盐和丙酮酸盐抑制组蛋白脱乙酰酶（HDAC）的能力有关。SLC 5A 8在迄今为止研究的大多数组织中作为肿瘤抑制因子发挥作用，并提供了与瓦尔堡效应的分子联系，沃伯格效应是大多数癌症的特征。它还将结肠细菌和膳食纤维与宿主联系起来。SLC 26 A3作为肿瘤抑制因子仅限于结肠;它是一种肿瘤抑制因子。 交换器，促进流出。SLC 26 A3的肿瘤抑制功能的可能机制与细胞内pH调节有关。SLC 39 A1是一种Zn 2+转运蛋白，其在前列腺肿瘤抑制中的作用已被证实。Zn ~（2+）在正常前列腺中以高浓度存在，在那里它发挥其肿瘤抑制功能。SLC 22 A18可能是一种有机阳离子转运蛋白，但其生理底物的身份尚不清楚。因此，没有关于负责该转运蛋白肿瘤抑制功能的分子途径的信息。将来可能会发现更多的SLC转运蛋白作为肿瘤抑制剂。
The role of plasma membrane transporters in cancer is receiving increasing attention in recent years. Several transporters for essential nutrients are up-regulated in cancer and serve as tumour promoters. Transporters could also function as tumour suppressors. To date, four transporters belonging to the SLC gene family have been identified as tumour suppressors. SLC5A8 is a Na+-coupled transporter for monocarboxylates. Among its substrates are the bacterial fermentation products butyrate and propionate and the ubiquitous metabolite pyruvate. The tumour-suppressive function of this transporter relates to the ability of butyrate, propionate and pyruvate to inhibit histone deacetylases (HDAC). SLC5A8 functions as a tumour suppressor in most tissues studied thus far, and provides a molecular link to Warburg effect, a characteristic feature in most cancers. It also links colonic bacteria and dietary fibre to the host. SLC26A3 as a tumour suppressor is restricted to colon; it is a exchanger, facilitating the efflux of . The likely mechanism for the tumour-suppressive function of SLC26A3 is related to intracellular pH regulation. SLC39A1 is a Zn2+ transporter and its role in tumour suppression has been shown in prostate. Zn2+ is present at high concentrations in normal prostate where it elicits its tumour-suppressive function. SLC22A18 is possibly an organic cation transporter, but the identity of its physiological substrates is unknown. As such, there is no information on molecular pathways responsible for the tumour-suppressive function of this transporter. It is likely that additional SLC transporters will be discovered as tumour suppressors in the future.