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

Nat Chem Biol. 2020 Apr;16(4):469-478. doi: 10.1038/s41589-020-0483-3. Epub 2020 Mar 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Neutral / genetics
  • Amino Acid Transport Systems, Neutral / metabolism
  • Antineoplastic Agents
  • Biochemical Phenomena
  • Biological Transport / genetics
  • Biological Transport / physiology
  • CRISPR-Cas Systems
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Drug Resistance / genetics*
  • Drug Resistance / physiology
  • Genetic Testing
  • Humans
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • Protein Transport / physiology
  • Solute Carrier Proteins / metabolism*
  • Solute Carrier Proteins / physiology
  • Symporters / genetics
  • Symporters / metabolism


  • Amino Acid Transport Systems, Neutral
  • Antineoplastic Agents
  • Cation Transport Proteins
  • Monocarboxylic Acid Transporters
  • Monosaccharide Transport Proteins
  • SLC38A5 protein, human
  • Solute Carrier Proteins
  • Symporters
  • UDP-galactose translocator
  • monocarboxylate transport protein 1
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2