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Deficiency of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis
Name
40170_2020_Article_232.pdf
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2.58 MB
Format
Adobe PDF
Checksum (MD5)
c30566eca8cb5ceee58a31fa40a31dd7
Author(s)
Alkan, H. F
Vesely, Paul W
Hackl, Hubert
Foßelteder, Johannes
Schmidt, Daniel R
Vander Heiden, Matthew G
Pichler, Martin
Hoefler, Gerald
Bogner-Strauss, Juliane G
Date Issued
November 26, 2020
Publisher
BioMed Central
Citation
Cancer & Metabolism. 2020 Nov 26;8(1):26
Version
Final published version
Abstract
Abstract
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+/NADH ratio, mitochondrial respiration, and tumor growth. Here, we report the impact of AGC1-knockdown on metastasis.
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
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.
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Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1186/s40170-020-00232-7
