In this paper, we show that the amino acid transporter ASCT2 (SLC1A5) is the primary importer of serine in cancer cells. While ASCT2 is well known as a glutamine transporter in cancer, Conger and team show that serine and glutamine compete for uptake through ASCT2. ASCT2-mediated serine uptake is essential for purine nucleotide biosynthesis and estrogen receptor α (ERα) promotes serine uptake by directly activating SLC1A5 transcription. Furthermore, inhibition of serine uptake via genetic KO of SLC1A5 combined with a low serine diet strongly reduces tumor growth in a luminal breast cancer mouse model.

We contributed to this work by running unbiased CRISPRi/a transporter screens in luminal breast cancer cells to determine the major serine importers. In both sets of screens, we found SLC1A5 as the top hit clearly showing its importance for serine import at growth limiting concentrations of serine.

Congrats to first author Kelly Conger, Jon Coloff, and all authors!

https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00881-7