Numerous mechanisms to support cells under conditions of transient nutrient starvation have been described. Several functions of the tumor-suppressor protein p53 can contribute to the adaptation of cells to metabolic stress and help cancer cell survival under nutrient-limiting conditions. We show here that p53 promotes the expression of SLC1A3, an aspartate/glutamate transporter that allows the utilization of aspartate to support cells in the absence of extracellular glutamine. Under glutamine deprivation, SLC1A3 expression maintains electron transport chain and tricarboxylic acid cycle activity, promoting de novo glutamate, glutamine, and nucleotide synthesis to rescue cell viability. Tumor cells with high levels of SLC1A3 expression are resistant to glutamine starvation, and SLC1A3 depletion retards the growth of these cells in vitro and in vivo, suggesting a therapeutic potential for SLC1A3 inhibition.
Pubmed ID: 30122553 RIS Download
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View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionslaboratory mouse with name BALB/cAnNCrl from MGI.
View all literature mentionsCell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line p53HCT116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-375 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SiHa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis monoclonal targets Glutamine Synthetase
View all literature mentionsThis monoclonal targets Human GOT2
View all literature mentionsThis monoclonal targets detection of MDM2, MDM2 p60 cleavage product and p53-MDM2 complexes
View all literature mentionsThis unknown targets Raised against a peptide mapping at the carboxy terminus of human p21
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets Phospho-p53 (Ser15)
View all literature mentionsThis monoclonal targets EAAT1 (D20D5) Rabbit mAb
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets Phospho-p53 (Ser15)
View all literature mentionsThis unknown targets Raised against a peptide mapping at the carboxy terminus of human p21
View all literature mentionsThis monoclonal targets Human GOT2
View all literature mentionsThis monoclonal targets detection of MDM2, MDM2 p60 cleavage product and p53-MDM2 complexes
View all literature mentionsThis monoclonal targets Glutamine Synthetase
View all literature mentionsThis monoclonal targets EAAT1 (D20D5) Rabbit mAb
View all literature mentions