A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs
- Author(s)
- Enrico Girardi, Adrián César-Razquin, Sabrina Lindinger, Konstantinos Papakostas, Justyna Konecka, Jennifer Hemmerich, Stefanie Kickinger, Felix Kartnig, Bettina Gürtl, Kristaps Klavins, Vitaly Sedlyarov, Alvaro Ingles-Prieto, Giuseppe Fiume, Anna Koren, Charles-Hugues Lardeau, Richard Kumaran Kandasamy, Stefan Kubicek, Gerhard F Ecker, Giulio Superti-Furga
- Abstract
Solute carriers (SLCs) are the largest family of transmembrane transporters in humans and are 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 screened compounds 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.
- Organisation(s)
- External organisation(s)
- Österreichische Akademie der Wissenschaften (ÖAW), ViruSure GmbH, Norwegian University of Science and Technology (NTNU) , Medizinische Universität Wien
- Journal
- Nature Chemical Biology
- Volume
- 16
- Pages
- 469–478
- No. of pages
- 10
- ISSN
- 1552-4450
- DOI
- https://doi.org/10.1038/s41589-020-0483-3
- Publication date
- 03-2020
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106001 General biology
- Keywords
- ASJC Scopus subject areas
- Molecular Biology, Cell Biology
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/55dc0828-b3d2-44f0-b829-00c5a00f09b1