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SLC1A5变体可用于癌细胞代谢重编程
2019-12-20 15:28

韩国延世大学药学院Jung Min Han研究组提出SLC1A5的一个变体是线粒体谷氨酰胺转运蛋白,用于癌细胞的代谢重编程。相关论文发表在2019年12月19日的《细胞—代谢》杂志上。

他们表示SLC1A5变体通过将谷氨酰胺转运到线粒体中在癌症代谢重编程中发挥关键作用。 SLC1A5变体含有一段线粒体定位的N端靶向信号。低氧诱导的SLC1A5变体的基因表达是由HIF-2α介导的。SLC1A5变体的过表达介导谷氨酰胺诱导的ATP产生和谷胱甘肽合成,并赋予吉西他滨对胰腺癌细胞的抗性。SLC1A5变体的敲低和过度表达改变癌细胞和肿瘤的生长,具有致癌作用。

这项工作表明SLC1A5变体是一个癌症代谢重编程过程中的线粒体谷氨酰胺转运蛋白。

据了解,谷氨酰胺是调节癌细胞中能量产生、氧化还原稳态和信号传导的必需营养素。尽管谷氨酰胺在线粒体代谢中很重要,但很长一段时间线粒体谷氨酰胺转运蛋白并不为人所熟知。

附:英文原文

Title: A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells

Author: Hee Chan Yoo, Seung Joon Park, Miso Nam, Juwon Kang, Kibum Kim, Joo Hye Yeo, Joon-Ki Kim, Yunkyung Heo, Hee Seung Lee, Myeong Youl Lee, Chang Woo Lee, Jong Soon Kang, Yun-Hee Kim, Jinu Lee, Junjeong Choi, Geum-Sook Hwang, Seungmin Bang, Jung Min Han

Issue&Volume: December 19, 2019

Abstract: Glutamine is an essential nutrient that regulates energy production, redox homeostasis,and signaling in cancer cells. Despite the importance of glutamine in mitochondrialmetabolism, the mitochondrial glutamine transporter has long been unknown. Here, weshow that the SLC1A5 variant plays a critical role in cancer metabolic reprogrammingby transporting glutamine into mitochondria. The SLC1A5 variant has an N-terminaltargeting signal for mitochondrial localization. Hypoxia-induced gene expression ofthe SLC1A5 variant is mediated by HIF-2α. Overexpression of the SLC1A5 variant mediatesglutamine-induced ATP production and glutathione synthesis and confers gemcitabineresistance to pancreatic cancer cells. SLC1A5 variant knockdown and overexpressionalter cancer cell and tumor growth, supporting an oncogenic role. This work demonstratesthat the SLC1A5 variant is a mitochondrial glutamine transporter for cancer metabolicreprogramming.

DOI: 10.1016/j.cmet.2019.11.020

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30664-3

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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