Deficiency of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis

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 impo...

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Main Authors: Alkan, H. Furkan (Author), Vesely, Paul W (Author), Hackl, Hubert (Author), Foßelteder, Johannes (Author), Schmidt, Daniel (Author), Vander Heiden, Matthew G. (Author), Pichler, Martin (Author), Hoefler, Gerald (Author), Bogner-Strauss, Juliane G (Author)
Other Authors: Koch Institute for Integrative Cancer Research at MIT (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor)
Format: Article
Language:English
Published: BioMed Central, 2022-07-15T19:34:57Z.
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Online Access:Get fulltext
LEADER 02108 am a22002533u 4500
001 131944.2
042 |a dc 
100 1 0 |a Alkan, H. Furkan  |e author 
100 1 0 |a Koch Institute for Integrative Cancer Research at MIT  |e contributor 
100 1 0 |a Massachusetts Institute of Technology. Department of Biology  |e contributor 
700 1 0 |a Vesely, Paul W  |e author 
700 1 0 |a Hackl, Hubert  |e author 
700 1 0 |a Foßelteder, Johannes  |e author 
700 1 0 |a Schmidt, Daniel  |e author 
700 1 0 |a Vander Heiden, Matthew G.  |e author 
700 1 0 |a Pichler, Martin  |e author 
700 1 0 |a Hoefler, Gerald  |e author 
700 1 0 |a Bogner-Strauss, Juliane G  |e author 
245 0 0 |a Deficiency of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis 
260 |b BioMed Central,   |c 2022-07-15T19:34:57Z. 
856 |z Get fulltext  |u https://hdl.handle.net/1721.1/131944.2 
520 |a 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. 
546 |a en 
655 7 |a Article