The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors
Open accessAbstract
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.
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Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
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Dixon, S. J., Winter, G. E., Musavi, L. S., Lee, E. D., Snijder, B., Rebsamen, M., Superti-Furga, G., & Stockwell, B. R. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00245 · Cited by 1,043
Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides
Birsoy, K., Possemato, R., Lorbeer, F. K., Bayraktar, E. C., Thiru, P., Yucel, B., Wang, T., Chen, W. W., Clish, C. B., & Sabatini, D. M. (2014) · Nature · doi:10.1038/nature13110 · Cited by 710
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Metadata
- Authors
- Birsoy, K., Wang, T., Possemato, R., Yilmaz, O. H., Koch, C. E., Chen, W. W., Hutchins, A. W., Gultekin, Y., Peterson, T. R., Carette, J. E., Brummelkamp, T. R., Clish, C. B., & Sabatini, D. M.
- Venue
- Nature Genetics
- Published
- 2012-12-02
- Volume
- 45
- Issue
- 1
- Pages
- 104-108
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2081651784
- Cited by
- 228
- References
- 5
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- green
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