MassIVE MSV000093916

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FGFR inhibition blocks NF-kappaB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma

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Description

This study explored the response to FGFR inhibition in FGFR2-fusion+ intrahepatic cholangiocarcinoma. We conducted phosphoproteomics experiments in a patient-derived FGFR2-driven ICC cell line model upon FGFR inhibition. Samples were treated with the FGFR inhibitor, Futibatinib/TAS120 (75 nM) for 4 or 24 hours or with DMSO vehicle. The experiments were done using an Orbitrap Fusion Lumos mass spectrometer. Multiplexing was achieved using either TMT10/11 reagents and the SPS-MS3 method. Basic pH reversed-phase chromatography (bRPLC) was used for off-line pre-fractionation; 12 fractions were analyzed for proteome mappings (PMID: 26700037) and 24 fractions plus a phosphotyrosine-enriched sample for phosphoproteome mappings (PMID: 31606085). Phosphoproteome mappings were done using both HCD fragmentation with Orbitrap fragment ion detection and CID fragmentation with ion trap fragment ion detection (PMID: 29487189, PMID: 31606085). Labeling scheme: 126: DMSO-1, ICC13-7 cells were treated with DMSO, replicate 1 127n: Futibatinib(TAS120)-4h-1, ICC13-7 cells were treated with Futibatinib (TAS120) for 4h, replicate 1 127c: Futibatinib(TAS120)-24h-1, ICC13-7 cells were treated with Futibatinib (TAS120) for 24h, replicate 1 128n: DMSO-2, ICC13-7 cells were treated with DMSO, replicate 2 128c: Futibatinib(TAS120)-4h-2, ICC13-7 cells were treated with Futibatinib (TAS120) for 4h, replicate 2 129n: Futibatinib(TAS120)-24h-2, ICC13-7 cells were treated with Futibatinib (TAS120) for 24h, replicate 2 [doi:10.25345/C5474729T] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: phosphoproteomics, cancer, cholangiocarcinoma, metabolism, FGFR, FGFR2 inhibitor, TMT11, Orbitrap Fusion Lumos

Contact

Principal Investigators:
(in alphabetical order) 		Nabeel Bardeesy, Massachusetts General Hospital and Harvard Medical School, Boston, USA
Wilhelm Haas, Massachusetts General Hospital and Harvard Medical School, United States
Submitting User: whaas
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