A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs

Autor: Stefanie Kickinger, Jennifer Hemmerich, Gerhard F. Ecker, Stefan Kubicek, Bettina Gürtl, Charles-Hugues Lardeau, Adrián César-Razquin, Giulio Superti-Furga, Richard Kumaran Kandasamy, Kristaps Klavins, Vitaly Sedlyarov, Alvaro Ingles-Prieto, Giuseppe Fiume, Sabrina Lindinger, Felix Kartnig, Konstantinos Papakostas, Anna Koren, Enrico Girardi, Justyna Konecka
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Nature chemical biology
Nature Chemical Biology
ISSN: 1552-4469
1552-4450
Popis: Solute Carriers (SLCs) represent the largest family of transmembrane transporters in humans and constitute major determinants of cellular metabolism. Several SLCs have been shown to be required for the uptake of chemical compounds into cellular systems, but systematic surveys of transporter-drug relationships in human cells are currently lacking. We performed a series of genetic screens in a haploid human cell line against 60 cytotoxic compounds representative of the chemical space populated by approved drugs. By using an SLC-focused CRISPR/Cas9 library, we identified transporters whose absence induced resistance to the drugs tested. This included dependencies involving the transporters SLC11A2/SLC16A1 for artemisinin derivatives and SLC35A2/SLC38A5 for cisplatin. The functional dependence on SLCs observed for a significant proportion of the compounds screened suggests a widespread role for SLCs in the uptake and cellular activity of cytotoxic drugs and provides an experimentally validated set of SLC-drug associations for a number of clinically relevant compounds.
Databáze: OpenAIRE
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