2. Academic Validation
  3. Deletion of Amino Acid Transporter ASCT2 (SLC1A5) Reveals an Essential Role for Transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to Sustain Glutaminolysis in Cancer Cells

Deletion of Amino Acid Transporter ASCT2 (SLC1A5) Reveals an Essential Role for Transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to Sustain Glutaminolysis in Cancer Cells

  • J Biol Chem. 2016 Jun 17;291(25):13194-205. doi: 10.1074/jbc.M115.700534.
Angelika Bröer 1,  Farid Rahimi 1,  Stefan Bröer 2
Affiliations

Affiliations

  • 1 From the Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
  • 2 From the Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia [email protected].
PMID: 27129276 DOI: 10.1074/jbc.M115.700534
Abstract

Many Cancer cells depend on glutamine as they use the glutaminolysis pathway to generate building blocks and energy for anabolic purposes. As a result, glutamine transporters are essential for Cancer growth and are potential targets for Cancer chemotherapy with ASCT2 (SLC1A5) being investigated most intensively. Here we show that HeLa epithelial cervical Cancer cells and 143B osteosarcoma cells express a set of glutamine transporters including SNAT1 (SLC38A1), SNAT2 (SLC38A2), SNAT4 (SLC38A4), LAT1 (SLC7A5), and ASCT2 (SLC1A5). Net glutamine uptake did not depend on ASCT2 but required expression of SNAT1 and SNAT2. Deletion of ASCT2 did not reduce cell growth but caused an amino acid starvation response and up-regulation of SNAT1 to replace ASCT2 functionally. Silencing of GCN2 in the ASCT2(-/-) background reduced cell growth, showing that a combined targeted approach would inhibit growth of glutamine-dependent Cancer cells.

Keywords

amino acid transport; cell growth; glutamine; mammalian target of rapamycin (mTOR); membrane transport.

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