Journal article
Tumor microenvironment promotes dicarboxylic acid carrier-mediated transport of succinate to fuel prostate cancer mitochondria
American journal of cancer research, v 5(5), pp 1665-1679
15 Apr 2015
PMID: 26175936
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Prostate cancer cells reprogram their metabolism, so that they support their elevated oxidative phosphorylation and promote a cancer friendly microenvironment. This work aimed to explore the mechanisms that cancer cells employ for fueling themselves with energy rich metabolites available in interstitial fluids. The mitochondria oxidative phosphorylation in metastatic prostate cancer DU145 cells and normal prostate epithelial PrEC cells were studied by high-resolution respirometry. An important finding was that prostate cancer cells at acidic pH 6.8 are capable of consuming exogenous succinate, while physiological pH 7.4 was not favorable for this process. Using specific inhibitors, it was demonstrated that succinate is transported in cancer cells by the mechanism of plasma membrane Na
+
-dependent dycarboxylic acid transporter NaDC3 (
SLC13A3 gene
). Although the level of expression of
SLC13A3
was not significantly altered when maintaining cells in the medium with lower pH, the respirometric activity of cells under acidic condition was elevated in the presence of succinate. In contrast, normal prostate cells while expressing NaDC3 mRNA do not produce NaDC3 protein. The mechanism of succinate influx via NaDC3 in metastatic prostate cancer cells could yield a novel target for anti-cancer therapy and has the potential to be used for imaging-based diagnostics to detect non-glycolytic tumors.
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Details
- Title
- Tumor microenvironment promotes dicarboxylic acid carrier-mediated transport of succinate to fuel prostate cancer mitochondria
- Creators
- Aigul Zhunussova - Department of Surgery, Drexel University College of Medicine Al-Farabi Kazakh National UniversityBhaswati Sen - Drexel UniversityLeah Friedman - Department of Surgery, Drexel University College of MedicineSultan Tuleukhanov - Al-Farabi Kazakh National UniversityAri D Brooks - Department of Surgery, University of PennsylvaniaRichard Sensenig - Department of Surgery, University of PennsylvaniaZulfiya Orynbayeva - Drexel University
- Publication Details
- American journal of cancer research, v 5(5), pp 1665-1679
- Publisher
- e-Century Publishing Corporation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Surgery
- Web of Science ID
- WOS:000358364200008
- Other Identifier
- 991019168362204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology