G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells. This study found that TNBC patients displayed elevated plasma kisspeptin levels compared with healthy subjects. It also provides the first evidence that in addition to promoting tumor growth and metastasis in vivo, KISS1R-induced glutamine dependence of tumors. In addition, tracer-based metabolomics analyses revealed that KISS1R promoted glutaminolysis and nucleotide biosynthesis by increasing c-Myc and glutaminase levels, key regulators of glutamine metabolism. Overall, this study establishes KISS1R as a novel regulator of TNBC metabolism and metastasis, suggesting that targeting KISS1R could have therapeutic potential in the treatment of TNBC.
Date Issued
2020-02-07
Date Acceptance
2020-01-27
Citation
Cell Death and Disease, 2020, 11 (2)
ISSN
2041-4889
Publisher
Nature Publishing Group
Journal / Book Title
Cell Death and Disease
Volume
11
Issue
2
Copyright Statement
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution andreproductionin any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a linktotheCreativeCommons license,and indicate ifchanges were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicatedotherwise in a credit line to the material. Ifmaterial is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32034133
PII: 10.1038/s41419-020-2305-7
Subjects
0601 Biochemistry and Cell Biology
1112 Oncology and Carcinogenesis
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 106