We validated that the ASCT2 glutamine transporter, like LAT1 essential amino acid transporter, are anti-cancer targets. We also revised the generally accepted ASCT2 / LAT1 functional coupling model.
The CSM "Tumor Hypoxia and Metabolism" team is investigating the nutritional and oxidative stress of rapidly growing cancer cells (depletion of oxygen and nutrients in tumors). Glucose and amino acids required for energy and growth can only cross cell membranes through transport systems. Of the twenty or so amino acid transporters (AAs), two, including the LAT1 / CD98 complex facilitating the entry of essential AA, and ASCT2 carrying glutamine are overexpressed in a variety of cancers suggestive of 'Darwinian selection' offering a nutritional advantage to tumors. After demonstrating that the LAT1 transporter is an anti-cancer target (Cancer Res, 2016), we explored the ASCT2 glutamine transporter and revisited the LAT1 / ASCT2 functional coupling model generally accepted in the scientific community. We demonstrate by the CRISPR-Cas9 invalidation technique of the ASCT2 gene:
- that the import of glutamine via ASCT2 is crucial for tumor growth (colon, lung),
- that this action is independent of the functional coupling LAT1 / ASCT2.
Cormerais, Y., Massard, P. A., Vucetic, M., Giuliano, S., Tambutté, E., Durivault, J., ... & Pouyssegur, J. (2018). The glutamine transporter ASCT2 (SLC1A5) promotes tumor growth independently of the amino acid transporter LAT1 (SLC7A5). Journal of Biological Chemistry, jbc-RA117.