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Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis
Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381264/ https://www.ncbi.nlm.nih.gov/pubmed/28382174 http://dx.doi.org/10.7150/thno.18005 |
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author | Jiang, Yang Cao, Yuan Wang, Yongbin Li, Wei Liu, Xinyi Lv, Yixuan Li, Xiaoling Mi, Jun |
author_facet | Jiang, Yang Cao, Yuan Wang, Yongbin Li, Wei Liu, Xinyi Lv, Yixuan Li, Xiaoling Mi, Jun |
author_sort | Jiang, Yang |
collection | PubMed |
description | Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute carrier family 3, member 1 (SLC3A1), the cysteine carrier, tightly correlated with clinical stages and patients' survival. Elevated SLC3A1 expression accelerated the cysteine uptake and the accumulation of reductive glutathione (GSH), leading to reduced reactive oxygen species (ROS). ROS increased the stability and activity of PP2Ac, resulting in decreased AKT activity. Hence, SLC3A1 activated the AKT signaling through inhibiting PP2A phosphatase activity. Consistently, overexpression of SLC3A1 enhanced tumorigenesis of breast cancer cells, whereas blocking SLC3A1 either with specific siRNA or SLC3A1 specific inhibitor sulfasalazine suppressed tumor growth and also abolished dietary NAC-promoted tumor growth. Collectively, our data demonstrate that SLC3A1 promotes cysteine uptake and determines cellular response to antioxidant N-acetylcysteine, suggesting SLC3A1 is a potential therapeutic target for breast cancer. |
format | Online Article Text |
id | pubmed-5381264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-53812642017-04-05 Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis Jiang, Yang Cao, Yuan Wang, Yongbin Li, Wei Liu, Xinyi Lv, Yixuan Li, Xiaoling Mi, Jun Theranostics Research Paper Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute carrier family 3, member 1 (SLC3A1), the cysteine carrier, tightly correlated with clinical stages and patients' survival. Elevated SLC3A1 expression accelerated the cysteine uptake and the accumulation of reductive glutathione (GSH), leading to reduced reactive oxygen species (ROS). ROS increased the stability and activity of PP2Ac, resulting in decreased AKT activity. Hence, SLC3A1 activated the AKT signaling through inhibiting PP2A phosphatase activity. Consistently, overexpression of SLC3A1 enhanced tumorigenesis of breast cancer cells, whereas blocking SLC3A1 either with specific siRNA or SLC3A1 specific inhibitor sulfasalazine suppressed tumor growth and also abolished dietary NAC-promoted tumor growth. Collectively, our data demonstrate that SLC3A1 promotes cysteine uptake and determines cellular response to antioxidant N-acetylcysteine, suggesting SLC3A1 is a potential therapeutic target for breast cancer. Ivyspring International Publisher 2017-02-26 /pmc/articles/PMC5381264/ /pubmed/28382174 http://dx.doi.org/10.7150/thno.18005 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Jiang, Yang Cao, Yuan Wang, Yongbin Li, Wei Liu, Xinyi Lv, Yixuan Li, Xiaoling Mi, Jun Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis |
title | Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis |
title_full | Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis |
title_fullStr | Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis |
title_full_unstemmed | Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis |
title_short | Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis |
title_sort | cysteine transporter slc3a1 promotes breast cancer tumorigenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381264/ https://www.ncbi.nlm.nih.gov/pubmed/28382174 http://dx.doi.org/10.7150/thno.18005 |
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