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Aspartate in tumor microenvironment and beyond: Metabolic interactions and therapeutic perspectives

JW. Soon, MA. Manca, A. Laskowska, J. Starkova, K. Rohlenova, J. Rohlena

. 2024 ; 1870 (8) : 167451. [pub] 20240805

Language English Country Netherlands

Document type Journal Article, Review

Aspartate is a proteinogenic non-essential amino acid with several essential functions in proliferating cells. It is mostly produced in a cell autonomous manner from oxalacetate via glutamate oxalacetate transaminases 1 or 2 (GOT1 or GOT2), but in some cases it can also be salvaged from the microenvironment via transporters such as SLC1A3 or by macropinocytosis. In this review we provide an overview of biosynthetic pathways that produce aspartate endogenously during proliferation. We discuss conditions that favor aspartate uptake as well as possible sources of exogenous aspartate in the microenvironment of tumors and bone marrow, where most available data have been generated. We highlight metabolic fates of aspartate, its various functions, and possible approaches to target aspartate metabolism for cancer therapy.

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$a Aspartate is a proteinogenic non-essential amino acid with several essential functions in proliferating cells. It is mostly produced in a cell autonomous manner from oxalacetate via glutamate oxalacetate transaminases 1 or 2 (GOT1 or GOT2), but in some cases it can also be salvaged from the microenvironment via transporters such as SLC1A3 or by macropinocytosis. In this review we provide an overview of biosynthetic pathways that produce aspartate endogenously during proliferation. We discuss conditions that favor aspartate uptake as well as possible sources of exogenous aspartate in the microenvironment of tumors and bone marrow, where most available data have been generated. We highlight metabolic fates of aspartate, its various functions, and possible approaches to target aspartate metabolism for cancer therapy.
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$a Starkova, Julia $u CLIP (Childhood Leukaemia Investigation Prague), Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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$a Rohlenova, Katerina $u Institute of Biotechnology of the Czech Academy of Sciences, Prumyslova 595, 252 50 Vestec, Prague-West, Czech Republic. Electronic address: katerina.rohlenova@ibt.cas.cz
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$a Rohlena, Jakub $u Institute of Biotechnology of the Czech Academy of Sciences, Prumyslova 595, 252 50 Vestec, Prague-West, Czech Republic. Electronic address: jakub.rohlena@ibt.cas.cz
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