Deficiency of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis.
AGC1
Aralar
Aspartate
Malate-Aspartate Shuttle
Metastasis
SLC25A12
Journal
Cancer & metabolism
ISSN: 2049-3002
Titre abrégé: Cancer Metab
Pays: England
ID NLM: 101607582
Informations de publication
Date de publication:
26 Nov 2020
26 Nov 2020
Historique:
received:
11
05
2020
accepted:
01
11
2020
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
10
12
2020
Statut:
epublish
Résumé
Aspartate biosynthesis and its delivery to the cytosol can be crucial for tumor growth in vivo. However, the impact of intracellular aspartate levels on metastasis has not been studied. We previously described that loss-of-aspartate glutamate carrier 1 (SLC25A12 or AGC1), an important component of the malate-aspartate shuttle, impairs cytosolic aspartate levels, NAD Low AGC1 expression correlates with worse patient prognosis in many cancers. AGC1-knockdown in mouse lung carcinoma and melanoma cell lines leads to increased pulmonary metastasis following subcutaneous or intravenous injections, respectively. On the other hand, conventional in vitro metastasis assays show no indication of increased metastasis capacity of AGC1-knockdown cells. This study highlights that certain branches of metabolism impact tumor growth and tumor metastasis differently. In addition, it also argues that commonly known metastasis indicators, including EMT genes, cell migration, or colony formation, do not always reflect metastatic capacity in vivo.
Sections du résumé
BACKGROUND
BACKGROUND
Aspartate biosynthesis and its delivery to the cytosol can be crucial for tumor growth in vivo. However, the impact of intracellular aspartate levels on metastasis has not been studied. We previously described that loss-of-aspartate glutamate carrier 1 (SLC25A12 or AGC1), an important component of the malate-aspartate shuttle, impairs cytosolic aspartate levels, NAD
RESULTS
RESULTS
Low AGC1 expression correlates with worse patient prognosis in many cancers. AGC1-knockdown in mouse lung carcinoma and melanoma cell lines leads to increased pulmonary metastasis following subcutaneous or intravenous injections, respectively. On the other hand, conventional in vitro metastasis assays show no indication of increased metastasis capacity of AGC1-knockdown cells.
CONCLUSION
CONCLUSIONS
This study highlights that certain branches of metabolism impact tumor growth and tumor metastasis differently. In addition, it also argues that commonly known metastasis indicators, including EMT genes, cell migration, or colony formation, do not always reflect metastatic capacity in vivo.
Identifiants
pubmed: 33292758
doi: 10.1186/s40170-020-00232-7
pii: 10.1186/s40170-020-00232-7
pmc: PMC7690131
doi:
Types de publication
Journal Article
Langues
eng
Pagination
26Subventions
Organisme : Austrian Science Fund
ID : SFB LIPTOX F3018
Organisme : Austrian Science Fund FWF
ID : W 1226
Pays : Austria
Organisme : Austrian Science Fund
ID : W1226 DK "Metabolic and Cardiovascular Disease"
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA242379
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA1405141
Pays : United States
Organisme : Austrian Science Fund
ID : LipoLUNG (P 30968)
Organisme : NCI NIH HHS
ID : R35CA242379
Pays : United States
Organisme : European Research Council ()
ID : LipoCHEX (340896)
Organisme : Austrian Science Fund
ID : P27108
Organisme : NCI NIH HHS
ID : R01 CA168653
Pays : United States
Organisme : Lustgarten Foundation (US)
ID : SU2C
Organisme : NCATS NIH HHS
ID : KL2 TR002542
Pays : United States
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