G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer.
Adult
Aged
Animals
Carcinogenesis
/ genetics
Case-Control Studies
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cellular Reprogramming
Energy Metabolism
Female
Gene Expression Regulation, Neoplastic
Glutaminase
/ genetics
Glutamine
/ metabolism
Humans
Mice, Inbred NOD
Mice, SCID
Middle Aged
Neoplasm Invasiveness
Nucleotides
/ metabolism
Proto-Oncogene Proteins c-myc
/ genetics
Receptors, Kisspeptin-1
/ genetics
Signal Transduction
Triple Negative Breast Neoplasms
/ genetics
Tumor Burden
Young Adult
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
07 02 2020
07 02 2020
Historique:
received:
31
07
2019
accepted:
27
01
2020
entrez:
9
2
2020
pubmed:
9
2
2020
medline:
10
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32034133
doi: 10.1038/s41419-020-2305-7
pii: 10.1038/s41419-020-2305-7
pmc: PMC7005685
doi:
Substances chimiques
KISS1R protein, human
0
MYC protein, human
0
Nucleotides
0
Proto-Oncogene Proteins c-myc
0
Receptors, Kisspeptin-1
0
Glutamine
0RH81L854J
Glutaminase
EC 3.5.1.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106Subventions
Organisme : NCI NIH HHS
ID : R01 CA224550
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA072720
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM055145
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA232246
Pays : United States
Organisme : CIHR
ID : PJT148823
Pays : Canada
Organisme : NCI NIH HHS
ID : R01 CA129536
Pays : United States
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