MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

Kivanç Birsoy, Tim Wang, Richard Possemato, Omer H. Yilmaz, Catherine E. Koch, Walter W. Chen, Amanda W. Hutchins, Yetis Gultekin, Tim R. Peterson, Jan E. Carette, Thijn R. Brummelkamp, Clary B. Clish, David M. Sabatini

Research output: Contribution to journalArticlepeer-review

175 Scopus citations


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.

Original languageEnglish
Pages (from-to)104-108
Number of pages5
JournalNature Genetics
Issue number1
StatePublished - Jan 2013


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