Mycielska, Maria E. and Dettmer, Katja and Ruemmele, Petra and Schmidt, Katharina and Prehn, Cornelia and Milenkovic, Vladimir M. and Jagla, Wolfgang and Madej, Gregor M. and Lantow, Margareta and Schladt, Moritz and Cecil, Alexander and Koehl, Gudrun E. and Eggenhofer, Elke and Wachsmuth, Christian J. and Ganapathy, Vadivel and Schlitt, Hans J. and Kunzelmann, Karl and Ziegler, Christine and Wetzel, Christian H. and Gaumann, Andreas and Lang, Sven A. and Adamski, Jerzy and Oefner, Peter J. and Geissler, Edward K. (2018) Extracellular Citrate Affects Critical Elements o Cancer Cell Metabolism and Supports Cancer Development In Vivo. CANCER RESEARCH, 78 (10). pp. 2513-2523. ISSN 0008-5472, 1538-7445
Full text not available from this repository. (Request a copy)Abstract
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 o 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. (C) 2018 AACR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROSTATE-CANCER; PROTEIN; TRANSPORT; DISEASE; HOMEOSTASIS; DISULFIRAM; GROWTH; LINE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2020 09:04 |
| Last Modified: | 23 Mar 2020 09:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14576 |
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