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http://purl.uniprot.org/citations/34662550http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34662550http://www.w3.org/2000/01/rdf-schema#comment"

Aims

Type 2 diabetes mellitus (T2DM) is a risk factor for breast cancer initiation and progression. Glutamine (GLN) is a critical nutrient for cancer cells. The aim of this study was to investigate the effect of T2DM-associated compounds upon GLN uptake by breast cancer cells.

Main methods

The in vitro uptake of 3H-GLN by breast cancer (MCF-7 and MDA-MB-231) and non-tumorigenic (MCF-12A) cell lines was measured.

Key findings

3H-GLN uptake in the three cell lines is mainly Na+-dependent and sensitive to the ASCT2 inhibitor GPNA. IFN-γ increased total and Na+-dependent 3H-GLN uptake in the two breast cancer cell lines, and insulin increased total and Na+-dependent 3H-GLN uptake in the non-tumorigenic cell line. GPNA abolished the increase in 3H-GLN uptake promoted by these T2DM-associated compounds. ASCT2 knockdown confirmed that the increase in 3H-GLN uptake caused by IFN-γ (in breast cancer cells) and by insulin (in non-tumorigenic cells) is ASCT2-dependent. IFN-γ (in MDA-MB-231 cells) and insulin (in MCF-12A cells) increased ASCT2 transcript and protein levels. Importantly, the pro-proliferative effect of IFN-γ in breast cancer cell lines was associated with an increase in 3H-GLN uptake which was GPNA-sensitive, blocked by ASCT2 knockdown and mediated by activation of the PI3K-, STAT3- and STAT1 intracellular signalling pathways.

Significance

IFN-γ and insulin possess pro-proliferative effects in breast cancer and non-cancer cell lines, respectively, which are dependent on an increase in ASCT2-mediated glutamine transport. Thus, an effective inhibition of ASCT2-mediated glutamine uptake may be a therapeutic strategy against human breast cancer in T2DM patients."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.org/dc/terms/identifier"doi:10.1016/j.lfs.2021.120054"xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/author"Silva C."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/author"Andrade N."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/author"Ferreira A.C."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/author"Martel F."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/author"Rodrigues I."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/author"Soares M.L."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/name"Life Sci"xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/pages"120054"xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/title"The pro-proliferative effect of interferon-gamma in breast cancer cell lines is dependent on stimulation of ASCT2-mediated glutamine cellular uptake."xsd:string
http://purl.uniprot.org/citations/34662550http://purl.uniprot.org/core/volume"286"xsd:string
http://purl.uniprot.org/citations/34662550http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34662550
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