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were subsequently analyzed using the ZIC-pHILIC LC-MS method described above. Quantification data was performed by Skyline (University of Washington) </p>MetaboLightsPublicLiquid Chromatography MS - alternating - hilic<p>Chromatographic separations were performed on a ZIC-pHILIC column (2.1 × 150 mm) at 30C and 0.15 mL/min, using 80% mobile phase B with a gradient to 20% B over 0.5–20.5 min, followed by re-equilibration.</p>Functional nutrient-genetic profiling reveals biotin and FBXW7 are essential to bypass glutamine addiction.Yifan LiuNortheastern UniversityK562mass spectrometry assay<p>cells were extracted by a mixed solution of 40% methanol, 40% acetonitrile and 20% water with 0.1M of formic acid on ice for 10mins then neutralized by 1.9M of ammonium bicarbonate.</p>Homo sapienshttps://www.ebi.ac.uk/metabolights/MTBLS13799Jourdain Alexis. University of Lausanne. Chemin des Boveresses 155, CP51 1066 Epalinges, Switzerland. alexis.jourdain@unil.ch.Miriam Lisci. University of Lausanne: Lausanne, Vaud, CH. University of Lausanne: Lausanne, Vaud, CH. miriam.lisci@unil.ch.<p>Extracts were subsequently analyzed using the ZIC-pHILIC LC-MS method described above. Quantification data was performed by Skyline (University of Washington) </p>Tracerliu.yifan7@northeastern.edu<p>k562 cells were treated by 13C glutamine and 15N glutamine separately then incubated at 37C from 0-24 hours. </p>Metabolomics<p>13C glutamine and 15N glutamine were treated to K562 cells incubated from 0-24 hours. then the cells were extracted and analyzed by LC-MS</p>Metabolomicstargeted metabolite profilinguntargeted metabolite profilingMetabolomicstargeted metabolite profilinguntargeted metabolite profiling<p>MS analysis was conducted in negative-mode SIM at 60,000 resolution (m/z 600–850). H-ESI conditions were: 3.2 kV spray voltage, sheath/aux/sweep gas 35/5/1, ion transfer tube 320 C, and vaporizer 175C</p>AsparatatefalseFunctional nutrient-genetic profiling reveals biotin and FBXW7 are essential to bypass glutamine addiction<p>Metabolic flexibility is key to survival and growth in all living organisms. In mammals, the pathways supporting cell proliferation in nutrient-limiting conditions have not been fully elucidated, although certain tumors display metabolic dependencies that can be targeted for therapy. Here, we combine metabolic tracers, nutrient supplementation, and genome-wide CRISPR-Cas9 screening to investigate the pathways mediating glutamine addiction, a hallmark of several cancers. We report that the vitamin biotin allows bypassing of glutamine dependence by activating pyruvate carboxylase (PC), and we discover a mechanism by which the tumor suppressor FBXW7 promotes pyruvate anaplerosis. Mechanistically, we show that FBXW7 prevents recruitment of a cluster of transcriptional repressors, including MNT and SIN3A, to the PC promoter, thereby maintaining PC expression and avoiding glutamine addiction. Our work sheds light on the molecular mechanisms that support metabolic flexibility and prevent glutamine addiction in cancer, with high relevance for FBXW7-associated cancer mutations. </p>2026-02-022026-01-28MTBLS13799