Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian target of rapamycin (mTOR) kinase, promotes glutamate secretion, cystine uptake, and incorporation into glutathione, linking growth factor receptor signaling with amino acid uptake and utilization. These results identify an unanticipated mechanism regulating amino acid metabolism in cancer, enabling tumor cells to adapt to changing environmental conditions.
Pubmed ID: 28648777 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsThis monoclonal targets SGK1
View all literature mentionsThis monoclonal targets 4F2hc/CD98
View all literature mentionsThis monoclonal targets xCT/SLC7A11
View all literature mentionsThis monoclonal targets Phospho-Akt Substrate (RXXS*/T*) (110B7E) Rabbit mAb (Magnetic Bead Conjugate)
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis monoclonal targets alpha-Tubulin antibody produced in mouse
View all literature mentionsThis monoclonal targets Actin
View all literature mentionsThis monoclonal targets IRS-1
View all literature mentionsThis polyclonal targets p-PKC alpha (Ser 657)
View all literature mentionsThis monoclonal targets 4E-BP1 (53H11) Rabbit mAb
View all literature mentionsThis monoclonal targets 4E-BP1, phospho (Thr37 / Thr46)
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein (54D2) Mouse mAb
View all literature mentionsThis monoclonal targets Phospho-S6 Ribosomal Protein (Ser235/236) (D57.2.2E) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-NDRG1 (Thr346) (D98G11) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Phospho-EGF Receptor (Tyr1068)
View all literature mentionsThis monoclonal targets Rictor (D16H9) Rabbit mAb
View all literature mentionsThis monoclonal targets Raptor (24C12) Rabbit mAb
View all literature mentionsThis unknown targets mTOR
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-373MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line T98G is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsA commercial graphing software company that offers scientific software for statistical analyses, curve fitting and data analysis. It offers four programs: Prism, InStat, StatMate and QuickCalcs.
View all literature mentionsImaging software used to acquire and analyze images from specific Bio-Rad imaging systems. Users can analyze gel or blot features, capture optimized image data, and generate a report of the data. Image Lab software exclusively runs on the Gel Doc EZ imager, Gel Doc XR+ imaging system, ChemiDo MP, ChemiDoc XRS+ imaging systems, Criterion Stain Free imager, and the GS-900calibrated densitometer.
View all literature mentions