| Literature DB >> 31866442 |
Hee Chan Yoo1, Seung Joon Park2, Miso Nam3, Juwon Kang1, Kibum Kim2, Joo Hye Yeo1, Joon-Ki Kim4, Yunkyung Heo1, Hee Seung Lee5, Myeong Youl Lee6, Chang Woo Lee6, Jong Soon Kang6, Yun-Hee Kim4, Jinu Lee1, Junjeong Choi1, Geum-Sook Hwang3, Seungmin Bang5, Jung Min Han7.
Abstract
Glutamine is an essential nutrient that regulates energy production, redox homeostasis, and signaling in cancer cells. Despite the importance of glutamine in mitochondrial metabolism, the mitochondrial glutamine transporter has long been unknown. Here, we show that the SLC1A5 variant plays a critical role in cancer metabolic reprogramming by transporting glutamine into mitochondria. The SLC1A5 variant has an N-terminal targeting signal for mitochondrial localization. Hypoxia-induced gene expression of the SLC1A5 variant is mediated by HIF-2α. Overexpression of the SLC1A5 variant mediates glutamine-induced ATP production and glutathione synthesis and confers gemcitabine resistance to pancreatic cancer cells. SLC1A5 variant knockdown and overexpression alter cancer cell and tumor growth, supporting an oncogenic role. This work demonstrates that the SLC1A5 variant is a mitochondrial glutamine transporter for cancer metabolic reprogramming.Entities:
Keywords: ASCT2; HIF-2α; SLC1A5; SLC1A5 variant; cancer metabolism; gemcitabine resistance; glutamine; hypoxia; metabolic reprogramming; mitochondrial glutamine transporter
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Year: 2019 PMID： 31866442 DOI： 10.1016/j.cmet.2019.11.020
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287