Extracellular citrate affects critical elements of cancer cell metabolism and supports cancer development in vivo
| Autor: | Sven A. Lang, Peter J. Oefner, Cornelia Prehn, Margareta Lantow, Katharina Schmidt, Karl Kunzelmann, Gudrun E. Koehl, Maria E. Mycielska, Petra Rümmele, Jerzy Adamski, Vadivel Ganapathy, Moritz Schladt, Gregor M. Madej, Alexander Cecil, Christine Ziegler, Hans Juergen Schlitt, Christian H. Wetzel, Christian J. Wachsmuth, Vladimir M. Milenkovic, Elke Eggenhofer, Katja Dettmer, Wolfgang Jagla, Andreas Gaumann, E. K. Geissler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Fatty acid metabolism Cancer Citrate transport medicine.disease Citric acid cycle 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Oncology chemistry 030220 oncology & carcinogenesis Cancer cell medicine Extracellular Cancer research Glycolysis Fatty acid synthesis |
| Zdroj: | Cancer Res. 78, 2513-2523 (2018) |
| Popis: | 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. Cancer Res; 78(10); 2513–23. ©2018 AACR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|