Back to Search
Start Over
MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors.
- Source :
- Nature Genetics; Jan2013, Vol. 45 Issue 1, p104-108, 5p, 1 Diagram, 3 Graphs
- Publication Year :
- 2013
-
Abstract
- There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA-resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10614036
- Volume :
- 45
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 84461469
- Full Text :
- https://doi.org/10.1038/ng.2471