title: Deletion of Amino Acid Transporter ASCT2 (SLC1A5) Reveals an Essential Role for Transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to Sustain Glutaminolysis in Cancer Cells.
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.
authors.affiliation: From the Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Angelika
authors.initials: A
authors.lastname: Bröer
authors.affiliation: From the Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Farid
authors.initials: F
authors.lastname: Rahimi
authors.affiliation: From the Research School of Biology, The Australian National University, Canberra, Australian Capital Territory 2601, Australia Stefan.broeer@anu.edu.au.
authors.forename: Stefan
authors.identifier: 0000-0002-8040-1634
authors.initials: S
authors.lastname: Bröer
mesh_terms: D026924:Amino Acid Transport System A / Q000502:physiology*; D026962:Amino Acid Transport System ASC / Q000235:genetics*; D049109:Cell Proliferation; D017353:Gene Deletion; D015870:Gene Expression; D005973:Glutamine / Q000378:metabolism; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D017136:Ion Transport; D053858:Metabolic Networks and Pathways; D015778:Minor Histocompatibility Antigens
chemical_list: D026924:Amino Acid Transport System A; D026962:Amino Acid Transport System ASC; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human; C445761:SLC38A1 protein, human; C498797:SLC38A2 protein, human; D005973:Glutamine
keywords: amino acid transport; cell growth; glutamine; mammalian target of rapamycin (mTOR); membrane transport