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Faust"],"technology_type":["Mass Spectrometry","Bottom-up proteomics","Data-independent acquisition"],"software":["Not available"],"submitter_keywords":["Aml","Ip-ms","Leukemia","Msln"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD067844"],"tissue":["Acute Myeloid Leukemia Cell Line"],"sample_protocol":["FASP Methods – Orbitrap Exploris DIA  Protein samples were reduced, alkylated, and digested on-bead using filter-aided sample preparation [Nature Methods 6: 359-62 (2009)] with sequencing grade modified porcine trypsin (Promega). Tryptic peptides were then separated by reverse phase XSelect CSH C18 2.5 um resin (Waters) on an in-line 150 x 0.075 mm column using an UltiMate 3000 RSLCnano system (Thermo). Peptides were eluted using a 60 min gradient from 98:2 to 65:35 buffer A:B ratio. Eluted peptides were ionized by electrospray (2.2 kV) followed by mass spectrometric analysis on an Orbitrap Exploris 480 mass spectrometer (Thermo). To assemble a chromatogram library, six gas-phase fractions were acquired on the Orbitrap Exploris with 4 m/z DIA spectra (4 m/z precursor isolation windows at 30,000 resolution, normalized AGC target 100%, maximum inject time 66 ms) using a staggered window pattern from narrow mass ranges using optimized window placements. Precursor spectra were acquired after each DIA duty cycle, spanning the m/z range of the gas-phase fraction (i.e. 496-602 m/z, 60,000 resolution, normalized AGC target 100%, maximum injection time 50 ms). For wide-window acquisitions, the Orbitrap Exploris was configured to acquire a precursor scan (385-1015 m/z, 60,000 resolution, normalized AGC target 100%, maximum injection time 50 ms) followed by 50x 12 m/z DIA spectra (12 m/z precursor isolation windows at 15,000 resolution, normalized AGC target 100%, maximum injection time 33 ms) using a staggered window pattern with optimized window placements. Precursor spectra were acquired after each DIA duty cycle.  Buffer A = 0.1% formic acid, 0.5% acetonitrile Buffer B = 0.1% formic acid, 99.9% acetonitrile"],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["Following data acquisition, data were searched using an empirically corrected library and a quantitative analysis was performed to obtain a comprehensive proteomic profile. Proteins were identified and quantified using EncyclopeDIA (Searle et al.) and visualized with Scaffold DIA using 1% false discovery thresholds at both the protein and peptide level. Protein exclusive intensity values were assessed for quality using ProteiNorm (Graw et al.). The MS2 exclusive intensities were normalized using global robust linear regression normalization (RLR) (Chawade et al.). Statistical analysis was performed using linear models for microarray data (limma) with empirical Bayes (eBayes) smoothing to the standard errors (Ritchie et al.). Proteins with an FDR adjusted p-value < 0.05 and an absolute fold change > 2 were considered significant."],"omics_type":["Proteomics"],"labhead":["Sonali P. Barwe, PhD"],"instrument_platform":[""],"submission_type":["COMPLETE"],"labhead_affiliation":["Nemours Children’s Hospital, DE"],"species":["Homo Sapiens (human)"],"publication":["41866035 Faust JR, Hamill D, Kolb EA, Stevens AM, Gopalakrishnapillai A, Barwe SP. Mesothelin promotes acute myeloid leukemia progression through LYN-dependent signaling. J Biol Chem. 2026 302(5):111390 10.1016/j.jbc.2026.111390"],"submitter_mail":["josh.faust@nemours.org"],"submitter_affiliation":["Nemours Children's Hospital"],"submitter_country":["United States"],"doi":["10.6019/PXD067844"],"pubmed_abstract":["Mesothelin (MSLN) is a glycosylphosphatidylinositol-anchored cell surface protein that is overexpressed in several solid tumors and in one-third of pediatric acute myeloid leukemia (AML) cases. It represents a validated immunotherapeutic target owing to its lack of expression in normal bone marrow. The function of MSLN in AML is unknown, but it is implicated to regulate adhesion in solid tumors through interaction with its only known binding partner, MUC16/CA125. This study uses CRISPR/Cas9 mutagenesis to generate knockout (KO) of MSLN in NOMO-1 and a MSLN-expressing patient-derived xenograft model to investigate its biological role in AML. We show that MSLN-KO cells proliferate slower, have reduced mitochondrial metabolism, are arrested in G1 cell cycle phase, adhere less to extracellular matrix in vitro and engraft slower in vivo. MSLN-KO cells also exhibit increased sensitivity to Ara-C and reduced extracellular matrix-mediated chemoprotection. Using an unbiased approach, we identify Src-family kinase member LYN, and guanine nucleotide-binding protein G(i) alpha subunit proteins, GNAI1, GNAI2, and GNAI3 as novel binding partners of MSLN in AML and show that pharmacological or genetic inhibition of LYN signaling restores NOMO-1 cell sensitivity to Ara-C. Together, these findings demonstrate that MSLN functions as an oncogenic driver in AML and reveal a previously unrecognized MSLN-LYN signaling axis, the therapeutic targeting of which may enhance responses to chemotherapy."],"pubmed_title":["Mesothelin promotes acute myeloid leukemia progression through LYN-dependent signaling."],"pubmed_authors":["Faust Joshua R JR, Hamill Darcy D, Kolb E Anders EA, Stevens Alexandra M AM, Gopalakrishnapillai Anilkumar A, Barwe Sonali P SP"],"additional_accession":[]},"is_claimable":false,"name":"Mesothelin Promotes Acute Myeloid Leukemia Cell Proliferation, Adhesion, and Chemoresistance via Novel Binding Partner Lyn","description":"MSLN has only been implicated to have one binding partner, MUC16/CA125. In an effort to identifying novel binding partners of MSLN, an IP-MS experiment was conducted using immunoprecipitations of MSLN in whole cell lysate of NOMO-1 and MSLN KO cells. We identified Src-family kinase member Lyn, and guanine nucleotide-binding protein G(i), alpha subunit proteins, GNAI1, GNAI2, and GNAI3 as a novel binding partners of MSLN in AML.","dates":{"publication":"2026-04-27","submission":"2025-08-28"},"accession":"PXD067844","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:35554","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","NEWT:1129","NEWT:309807","NEWT:55153","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:43186","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:1147161","NEWT:661410","NEWT:638632","NEWT:263737","NEWT:224326","NEWT:1333499","NCBITaxon:79857","NEWT:1096976","NEWT:5702","NEWT:95648","NEWT:1589","NEWT:135622","NEWT:1349","NEWT:35786","NEWT:1580","NEWT:96731","NEWT:383379","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:44491","NEWT:641809","NEWT:27933","NEWT:556484","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:3112","NEWT:79329","NEWT:4442","NEWT:192875","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:1316931","NEWT:224308","NEWT:3347","NEWT:511145","NEWT:160621","NEWT:212790","NEWT:931281","NEWT:4432","NEWT:5762","NEWT:5763","NEWT:658457","NEWT:1310161","NEWT:77133","NEWT:295358","NEWT:145481","NCBITaxon:79824","NEWT:2246","NEWT:2652724","NEWT:5757","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:44447","NEWT:752555","NEWT:498211","NEWT:5759","NEWT:1736231","NEWT:5518","NEWT:398007","NEWT:1392","NEWT:498217","NEWT:498216","NEWT:2242","NEWT:11320","NEWT:286","NEWT:391619","NEWT:246196","NEWT:287","NEWT:246197","NEWT:145458","NEWT:633149","NEWT:10239","NEWT:68895","NEWT:44685","NEWT:161934","NEWT:4897","NEWT:1148","NEWT:5744","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:55571","NEWT:35500","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:4896","NEWT:1287689","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:294","NEWT:1773","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:3711","NEWT:935293","NEWT:375146","NEWT:2065263","NEWT:1772","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:52283","NEWT:11988","NEWT:284812","NEWT:8175","NEWT:400667","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:3702","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:33548","NEWT:274","NEWT:7070","NCBITaxon:287","NEWT:408172","NEWT:408170","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1436733","NEWT:460519","NEWT:1247411","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:333760","NEWT:56636","NEWT:1513458","NEWT:1233681","NCBITaxon:40559","NEWT:506599","NEWT:2853422","NEWT:81077","NEWT:84588","NEWT:1679718","NEWT:480","NEWT:65349","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:300852","NEWT:1502","NEWT:376686","NEWT:95486","NEWT:508771","NEWT:1883446","NEWT:253","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:93062","NCBITaxon:4932","NEWT:109760","NEWT:943274","NEWT:644223","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:272623","NEWT:272624","NEWT:320637","NEWT:983964","NEWT:118499","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:1130798","NEWT:55529","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:1116234","NEWT:1255228","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:3983","NEWT:352472","NEWT:1071661","NEWT:1202532","NEWT:360094","NEWT:470","NEWT:41364","NEWT:1313","NEWT:1218097","NCBITaxon:50557","NEWT:39251","NEWT:39491","NCBITaxon:5811","NEWT:29491","NEWT:101841","NEWT:2014887","NEWT:33952","NEWT:153009","NEWT:261756","NEWT:571256","NEWT:40483","NEWT:63366","NEWT:63367","NEWT:688333","NEWT:215402","NCBITaxon:548681","NEWT:318586","NEWT:272634","NEWT:9031","NEWT:1872122","NEWT:1308","NEWT:7091","NEWT:1034015","NEWT:760568","NEWT:141262","NEWT:108931","NEWT:1055524","NEWT:4087","NEWT:9778","NEWT:306","NEWT:150475","NEWT:303","NEWT:267872","NEWT:97477","NEWT:7111","NEWT:347515","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:4090","NEWT:4092","NEWT:9541","NEWT:8694","NEWT:4093","NEWT:4096","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:941442","NEWT:536088","NEWT:13076","NEWT:1226408","NEWT:7108","NEWT:40479","NEWT:43989","NEWT:4076","NEWT:142615","NEWT:317","NEWT:1006581","NEWT:885318","NEWT:39488","NEWT:550","NEWT:4081","NEWT:273068","NEWT:554","NEWT:98334","NEWT:451516","NEWT:4084","NEWT:63577","NEWT:36185","NEWT:1225786","NEWT:7574","NEWT:1715256","NEWT:30640","NEWT:575412","NEWT:929793","NEWT:29204","NEWT:28112","NEWT:114155","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:6239","NEWT:162425","NEWT:216257","NEWT:102169","NEWT:9986","NEWT:4054","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8655","NEWT:5147","NEWT:98351","NEWT:12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