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Mycielska, M.E.* ; Dettmer, K.* ; Rümmele, P.* ; Schmidt, K.* ; Prehn, C. ; Milenkovic, V.M.* ; Jagla, W.* ; Madej, M.G.* ; Lantow, M.* ; Schladt, M.T.* ; Cecil, A. ; Koehl, G.E.* ; Eggenhofer, E.* ; Wachsmuth, C.J.* ; Ganapathy, V.* ; Schlitt, H.J.* ; Kunzelmann, K.* ; Ziegler, C.* ; Wetzel, C.H.* ; Gaumann, A.* ; Lang, S.A.* ; Adamski, J. ; Oefner, P.J.* ; Geissler, E.K.*

Extracellular citrate affects critical elements of cancer cell metabolism and supports cancer development in vivo.

Cancer Res. 78, 2513-2523 (2018)
Publ. Version/Full Text Postprint DOI
Open Access Green
Glycolysis and fatty acid synthesis are highly active in cancer cells through cytosolic citrate metabolism, with intracellular citrate primarily derived from either glucose or glutamine via the tricarboxylic acid cycle. We show here that extracellular citrate is supplied to cancer cells through a plasma membrane-specific variant of the mitochondrial citrate transporter (pmCiC). Metabolomic analysis revealed that citrate uptake broadly affected cancer cell metabolism through citrate-dependent metabolic pathways. Treatment with gluconate specifically blocked pmCiC and decreased tumor growth in murine xenografts of human pancreatic cancer. This treatment altered metabolism within tumors, including fatty acid metabolism. High expression of pmCiC was associated with invasion and advanced tumor stage across many human cancers. These findings support the exploration of extracellular citrate transport as a novel potential target for cancer therapy. Significance: Uptake of extracellular citrate through pmCiC can be blocked with gluconate to reduce tumor growth and to alter metabolic characteristics of tumor tissue.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Journal Cancer Research
Quellenangaben Volume: 78, Issue: 10, Pages: 2513-2523 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place Philadelphia, Pa.
Reviewing status Peer reviewed