Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/checksum.txtftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep3.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_IgG_coIP_L3.6pl_monolayer_rep1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_SMAD_coIP_L3.6pl_monolayer_rep1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_SMAD_coIP_L3.6pl_monolayer_rep2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_IgG_coIP_L3.6pl_monolayer_rep2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/RAW_IgG_coIP_ABCG2.L3.6pl_tumoursphere.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_SMAD_coIP_L3.6pl_monolayer_rep2.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_IgG_coIP_L3.6pl_monolayer_rep2.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep1.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_SMAD_coIP_L3.6pl_monolayer_rep1.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_IgG_coIP_L3.6pl_monolayer_rep1.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep3.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep2.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/PEAK_IgG_coIP_ABCG2.L3.6pl_tumoursphere.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_SMAD_coIP_L3.6pl_monolayer_rep2.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_IgG_coIP_L3.6pl_monolayer_rep2.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep3.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_IgG_coIP_L3.6pl_monolayer_rep1.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep1.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_PHF5A_coIP_ABCG2.L3.6pl_tumoursphere_rep2.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_IgG_coIP_ABCG2.L3.6pl_tumoursphere.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378/SEARCH_SMAD_coIP_L3.6pl_monolayer_rep1.datprimaryOK200siim.pauklin@ndorms.ox.ac.ukSiwei DengMass SpectrometryShotgun proteomicsAll-ion fragmentationPhf5a complexPancreatic cancerEpigeneticsKmt2a-wdr5 inhibitorCancer stem cellshttps://www.ebi.ac.uk/pride/archive/projects/PXD038378PancreasI. Co-immunoprecipitation For SMAD2/3 nuclear co-IP experiments, cells were pretreated with recombinant INHBA protein (R and D Systems, cat. 338-AC-050/CF) at a final concentration of 100 ng/ml for 24 hours. Nuclear protein complexes were extracted using the nuclear complex co-IP kit (Active Motif, cat. 54001) following the manufacturer’s instructions. Nuclear protein extracts were incubated with target-specific antibodies including anti-SMAD 2/3 (RRID:AB_2270778, R and D Systems, cat. AF3797), anti-PHF5A (RRID:AB_2165365, Proteintech, cat. 15554-1-AP), as well as isotype control antibodies including normal goat IgG (RRID:AB_354267, R and D Systems, cat. AB-108-C) and rabbit (DA1E) mAb IgG XP (RRID:AB_1550038, Cell Signaling Technology, cat. 3900S) for 2 hours at 4°C with agitation, followed by overnight incubation with Protein A/G Plus-agarose beads (Santa Cruz Biotechnology, cat. sc-2003) at 4°C with agitation. Agarose beads were washed 3 times with 1x PBS and then suspended in 1x Laemmli sample buffer supplemented with 2-mercaptoethanol (Sigma-Aldrich, cat. M6250) at a final concentration of 2.5%. Samples were boiled at 95°C for 5 minutes to elute co-immunoprecipitated proteins for western blotting and LC-MS/MS analysis. II. LC-MS/MS analysis LC-MS/MS analysis of co-IP protein samples was performed at the Cambridge Centre for Proteomics (Cambridge, UK) using a Dionex Ultimate 3000 RSLC nanoUPLC (Thermo Fisher Scientific Inc, Waltham, MA, USA) system and a Q Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific Inc, Waltham, MA, USA). Separation of peptides was performed by reverse-phase chromatography at a flow rate of 300 nl/min and a Thermo Scientific reverse-phase nano Easy-spray column (Thermo Scientific PepMap C18, 2 µm particle size, 100A pore size, 75 µm i.d. x 50 cm length). Peptides were loaded onto a pre-column (Thermo Scientific PepMap 100 C18, 5 µm particle size, 100A pore size, 300 µm i.d. x 5mm length) from the Ultimate 3000 autosampler with 0.1% formic acid for 3 minutes at a flow rate of 15 µl/min. After this period, the column valve was switched to allow the elution of peptides from the pre-column onto the analytical column. Solvent A was water + 0.1% formic acid and solvent B was 80% acetonitrile, 20% water + 0.1% formic acid. The linear gradient employed was 2-40% B in 90 minutes (the total run time including column washing and re-equilibration was 120 minutes). The LC eluant was sprayed into the mass spectrometer by means of an Easy-spray source (Thermo Fisher Scientific Inc.). All m/z values of eluting ions were measured in an Orbitrap mass analyzer, set at a resolution of 35000 and scanned between m/z 380-1500. Data dependent scans (Top 20) were employed to automatically isolate and generate fragment ions by higher energy collisional dissociation (HCD, Normalised collision energy (NCE):25%) in the HCD collision cell, and measurement of the resulting fragment ions was performed in the Orbitrap analyser, set at a resolution of 17500. Singly charged ions and ions with unassigned charge states were excluded from being selected for MS/MS and a dynamic exclusion of 60 seconds was employed.PrideNot availablePost-run, all MS/MS data were converted to mgf files which were then submitted to the Mascot search algorithm (Matrix Science, London UK, version 2.6.0) and searched against a common contaminants database (cRAP_20190401.fasta) and the UniProt human database (CCP_UniProt_homo sapiens_proteome_20180409 database (93734 entries)), assuming the digestion enzyme trypsin. Mascot was searched with a fragment ion mass tolerance of 0.100 Da and a parent ion tolerance of 20 PPM. Carbamidomethyl of cysteine was specified in Mascot as a fixed modification. Deamidation of asparagine and glutamine and oxidation of methionine were specified in Mascot as variable modifications. Scaffold (version Scaffold_4.10.0, Proteome Software Inc., Portland, OR) was used to validate MS/MS based peptide and protein identifications. Peptide identifications were accepted if they could be established at greater than 95.0% probability by the Peptide Prophet algorithm with Scaffold delta-mass correction. Protein identifications were accepted if they could be established at greater than 99.0% probability and contained at least 2 identified peptides. Protein probabilities were assigned by the Protein Prophet algorithm. Proteins that contained similar peptides and could not be differentiated based on MS/MS analysis alone were grouped to satisfy the principles of parsimony. Proteins sharing significant peptide evidence were grouped into clusters.ProteomicsSiim PauklinPARTIALBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UKHomo Sapiens (human)Not availablesiwei.deng@hotmail.comNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of OxfordUnited KingdomHTRX1, Ibraf, Feature, 4932409F11Rik, protein, Tumor, Pancreatic Neoplasm, prevention, CFAP89, Cxxc7, Productivity, HMGX1, dmTAF[[II]]230, protein polypeptide chains, relapse, Ca tail of pancreas, Ca head of pancreas, SF3b14b, Mother Cells, Relapses, protein aggregate, DXO, prevention and control, 2410008O07Rik, Gene Expressions, TFIID TAF250, reference sample, cel, entire life cycle, Recurrences, AA960360, proteins, Pancreatic Cancers, high grade, HMGXB1, Epigenomic, preventive measures, DNA Dependent RNA Polymerase II, Hmgxb1, 3.1.13.-, SMCR, Therapies, Malignancies, associated, Pancreatic Acinar Carcinomas, pancreatic tumour, pancreas neoplasm, Tumors, RGD1307829, Therapy, HEL-S-85p, Relapse, Carcinoma, dTAF[[II]]230, preventive therapy, DmelCG17437, Mll, MLL, malignant neoplasm of body of pancreas, HRX, familial, TAF200, TAFII-250, TAF250/230, zw8, TAFII250, Benign, Colony-Forming Unit, Stem Cell, Recrudescence, Chemotherapy, pancreatic carcinoma, Pancreatic, Cancer of the Pancreas, Carcinomas, Mother Cell, TET1-MLL, AA408785, Gt1, SAP14b, Cancer of Pancreas, SF3B7, 1200004E06Rik, Pharmacotherapy, DOM3Z, l(1)3Ad, RNA Pol II, Epigenetic, malignant neoplasm of head of pancreas, life, Stem, All1, WDSTS, Benign Neoplasms, Colony Forming Units, CG17603, Features, xwdr5, TAF[[II]], mKIAA4050, Pancreas, Pancreatic Acinar Carcinoma, Malignant Neoplasms, Big, Ca body of pancreas, Taf250, Patient, SR3-5, Cells, DOM3L, Epigenetics, PNCA, other neoplasm, bK223H9.2, Acinar Carcinomas, TAF230, 5730446A07Rik, 1110007B08Rik, d230, l(1)G0251, lifespan, chemotherapy, Neoplasms, l(1)16-94, Colony-Forming Units, Progenitor Cell, Benign Neoplasm, Pancreas Cancer, MLL|GAS7, Gene, dTAFII250, pancreas, pharmacotherapy, 3.6.1.-, Pharmacotherapies, protein-containing complex, Malignant, EfW1, Pancreas Cancers, MLL1A, Chemotherapies, WDS, Wds, Client., polypeptide chain, dmTAF1, Pancreatic Cancer, Taf230, Ac2-246, 1110001C23Rik, Gene Products, big-3, Pancreatic Acinar, SMS, attenuated, Drug Therapies, Progenitor, TAF250, Pancreatic Carcinomas, BIG-3, Taf200, dTAF[[II]]250, Malignancy, entire lifespan, Recrudescences, cell, Pancreatic Carcinoma, Acinar Carcinoma, RAI1, Rai1, ALL-1, inhibiteur, Mother, Taf1p, Big-3, Expressions, Mll1, MLL1, Neoplasias, dTAF250, rai1, RGD1564760, Dom-3 homolog Z, 6430520K01, inhibidor, Clients, Characteristics, Expression, TAF, EG:BACR25B3.7, Controlled, Cancer, inhibitors, Controlling, Colony Forming Unit, TAF[[II]]250, swd3, Malignant Neoplasm, protein complex, Progenitor Cells, pancreatic neoplasm, Proteins, zw-8, l(3)84Ab, inhibitor, BG:DS00004.13, WDR5, MLL/GAS7, NG6, Pancreas Neoplasm, Cell, dTAF230, Characteristic, wdr5, native protein, natural protein, p230, Protein, Neoplasm, TAF[[II]]250/230, TFIID, AA623952, Taf[[II]]250, RGD1563764, malignant neoplasm of tail of pancreas, pancreatic tumor, INI, AV297001, TAF[[II]]230, prophylaxis, CXXC7, Rds3, TAF[II]250, Cancers, Drug, 5730490E10Rik, Protein Gene Products, Gene Proteins, DmelCG17603, control, l(1)zw8, TRX1, RNA Polymerase B, pharmacologic therapy, SWD3, DNA-Dependent RNA Polymerase II, Pancreas Neoplasms, mKIAA0783, CG17437, Neoplasia, TAF1sodium salt, Water, ammonium formate, SMAD family member 2, Size, 13C-labeled, cadmium salt, MeCN, smad-2, PhrB photolyase activity, ion, NZW, Particle, H(2)O, ted, BOUND WATER, rabbit, magnesium formate, X-50, oxidane, zinc salt, heavy chain disease, Solvent, prevention, Long Term, WATER, HOH, l(1)AA33, 5730420M11Rik, dmTAF[[II]]230, Polypeptides, protein polypeptide chains, KL receptor activity, domestic cat, Domestic Cats, Gamma Globulin, cobalt(II) formate dihydrate, CH3-C#N, B1, neural nuclei, SCO5, 1, 2, 3, SCO1, 4, NUP96, Gsfsow3, Zealand Rabbit, 9, 2210418N07, epithelium, bacterial catalase-peroxidase activity, average, SET, pore, TFIID TAF250, cel, CT21282, JV18, proteins, SAP-1, W, SAP-2, Staphylococcal, EG:196F3.2, adult mouth, SUPPRESSOR OF AUXIN RESISTANCE 3, AI047805, DmelCG4299, set, 15-disilaoctadecane, haem catalase activity, C1 4B, column, l(1)B2/13.1, sample, D1, Bs, Precipitations, single organism signaling, nickel salt, AI315345, LC-MS2, equilase activity, dTAF[[II]]230, preventive therapy, l(1)LB9, BZRP, cobalt (+2) salt, Chinchilla, TAF200, Longterm Effect, Saposin-A, Parotid isoelectric focusing variant protein, antibodies, A330009E03Rik, PBS, PBR, Oral region, PBT, H2O, 11-tetrathia-4, sodium (4:1:1) salt, cavitas oris, Dm1, magnesium salt, Felis domestica, [4)-3, Sepharose C1, anatomische Mund, Sizes, dipyrimidine photolyase (photosensitive), XSmad2, Hydrogen Oxide, ACGNAT, pbt, Industrial, SF3B7, Industrial Arts, HLA-DR-associated protein II, DI-2, mMad2, Mad-related protein 2, Oral part of face, I-2Dm, formate, Capras, Oryctolagus cuniculus, cromium (+3), Mouth, valva (Spanish, Felis sylvestris catus, dsmad2, Chinchilla Rabbit, nuclear complex, I-2PP1, Painful bladder syndrome, TAF-IBETA, Taf250, Saposin-D, Saposin-C, Saposin-B, liquid chromatography-tandem mass spectroscopy, GT, cuniculus, vestibule of mouth, ammonium (4:1) salt, TAF-Ibeta, methyl cyanide, DmelCG32810, DROCATHPO, oral cavity, lead (+2) salt, bs36h11.y1, bK223H9.2, TAF230, krk1, BPBS, Particle Sizes, 2-ME, FRP, nickel formate dihydrate, Immunoglobulin, lead formate, Peptidomics, Effects, aluminum salt, tmp, protein-containing complex, abdominal muscles, thomson, CG7826, agua, mass-to-charge ratio, CrAT, manganese catalase activity, Ac2-246, Hare, LC-MSMS, Immune Precipitations, Gene Products, CG7835, CG42273, SMAD 2, CG2262, Immune Precipitation, DSmad2, Japanese white rabbit, anatomical systems, dTAF[[II]]250, Rabbit, Immunoglobulin GT, thallium (+1) salt, Longterm, cell, Smad-2, Dispersin, rubidium salt, smad2, F23A5.3, 2pp2a, pk18, Long-Term, methanoic acid, ions, MBR, CG10574, oral vestibule, dTAF250, DmelCG6871, Component C, goats, 2PP2A, dSET, dSet, PTBR, peptidos, Chromatographies, oral fissure, domestic goat, PTHB1, LB5, DmelCG2262, New, proto-oncogene c-Kit, DMCATHPO, heme catalase activity, 1-(14)C-labeled, Chinchilla Rabbits, Peptide P-C, Madh2, Proteins, BG:DS00004.13, potassium formate, Co-beta-glucosidase, copper (+2) salt, Rnt, acetonitrile, motif, buffer, Cell, dTAF230, lLB5, native protein, I-2PP2A, KIT ligand receptor activity, C18, Felis domesticus, cupric formate, chemical analysis, Long Term Effects, Dm I-2, Belgian, TAF[[II]]250/230, Carpa hircus, eagle-Barrett syndrome, aluminum formate, XKrk1, CS1, Taf[[II]]250, AU020952, RPE, lithium formate, ensemble, prophylaxis, New Zealand Rabbits, Polyglobin, CSAct, CG6871, pore-forming toxin activity, ethanenitrile, CD117, mDRC, Longterm Effects, ME-IV, p. pigmentosa retinae, Gene Proteins, domestic rabbit, Cerebroside sulfate activator, SMOX, signalling process, C-Kit, Protein C, Rima oris, control, Protein A, Ssm, xkl-1, 2-mercapto-, liquid chromatography tandem mass spectrometry, deoxyribonucleate pyrimidine dimer lyase (photosensitive), smox, [OH2], channel-forming toxin activity, liquid chromatography tandem mass spectroscopy, IgG Antibody, Co-Immunoprecipitations, IPP2A2, rabbits, NCMe, determination, Sepharose C1 4B, Parotid double-band protein, leg, Pa, zinc formate, Domestic Cat, Cs-1, lead salt, protein, Xkl-1, pigmented epithelium, 10, Co Immunoprecipitation, Ethanol, 15, Gsfsco1, ammonium tetraformate, peptido, exact), SF3b14b, Min, Sphingolipid activator protein 2, protein aggregate, Gsfsco5, prevention and control, Effect, A1 activator, DmelCG42273, SOW3, hSMAD2, MADH2, Salivary acidic proline-rich phosphoprotein 1|2, Sepharose, Pr1|Pr2, MS2., LCMSMS, Capra aegagrus hircus, reference sample, peptides, vestibulum oris, TAF-I, JV18-1, Co-Immunoprecipitation, mouth cavity, New Zealand White Rabbits, Precipitation, pigmented retina, 2 Mercaptoethanol, min, cluster of neural nuclei, mAPC, IBP, analyzer, Domestic, copper, DNA cyclobutane dipyrimidine photolyase activity, anatomical valve, preventive measures, South African angora goat, IGAAD, Immune, lithium salt, DmelCG10574, RUN, Run, 380, Mothers against DPP homolog 2, dihydridooxygen, Lepus cuniculus, Bladder pain syndrome, dihydrogen oxide, Sl, ammonium (2:1) salt, Long-Term Effects, catalase-peroxidase activity, 7120426M23Rik, phapii, PRE, European rabbit, 4B, Arts, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, LC-MS/MS, aqua, Dmel_CG7826, Domestic Rabbits, StF-IT-1, Tr-kit, Th, 2.3.1.7, TAFII-250, TAF250/230, Thermo Scientific, AI195249, AA33, Menstruation, TAFII250, catalase reaction, IgG3, HCD, IgG4, retinal pigment, Ionen, IgG1, dSMAD2, IgG2, l(1)G0348, DSMAD2, kl1-A, cavum oris, KIT, dSmad2, Oryctolagus, CG14784, nickel (+2) salt, GAT, retinal pigment layer, Capra, Dmel_CG7835, hMAD-2, 15-tetraethoxy-, CG14783, Mnb, MNB, tyrosine-protein kinase Kit, absence of, ammonium salt, SAP14b, Painful Bladder Syndrome, IgG, Sphingolipid activator protein 1, Parotid proline-rich protein 1|2, MS/MS, hydrogen-peroxide:hydrogen-peroxide oxidoreductase activity, cobaltous formate, hydrogen hydroxide, kit, CG4299, AW124434, Felis silvestris catus, CG17603, TAF[[II]], acqua, Biotechnologies, phr A photolyase activity, DNA-photoreactivating enzyme, SR3-5, IgG2A, 2-Mercaptoethanol, IgG2B, copper salt, Sepharose 4B, Polypeptide, Wasser, Db-F, i2pp2a, U00145, 7S, Bladder Pain Syndrome, 1110007B08Rik, Cas1, CG1849, Carnitine acetylase, d230, Belgian Hare, MADR2, Psychomotor agitation, cesium salt, SCF receptor activity, Gene, dTAFII250, 2-(1-benzyl-4-methylpyrazol-3-yloxy)-2-methylpropionic acid, photoreactivating enzyme activity, Goat, EfW1, PHAPII, LC-MS-MS, Buffer, formic acid, Db-s, Antibody, potassium salt, polypeptide chain, scfr, dmTAF1, goat, Taf230, mixt. with silica, 14C-labeled, Parotid acidic protein, stratum pigmentosa retinae, caperase activity, SCFR, valve, TAF250, Fdc, Taf200, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, IgG(T), PRECOCIOUS, Saposin-B-Val, iones, Runt, ipp2a2, CatA, CATA, Taf1p, eau, calcium formate, Madr2, New Zealand White Rabbit, SMAD2, Cats, MAD homolog 2, Catl, taf-ibeta, Agarose, pharyngeal valve, PIF-F, Smad2, cats, cromium (+3) salt, Long-Term Effect, TAF, PIF-S, 6-An-alpha-L-Galp-(1->3)-beta-D-Galp-(1->]n, F23A5_3, sodium formate, Controlled, Controlling, DYRK1, TAF[[II]]250, EDF, ng/ml, nickel formate, DBI, 3H-labeled, protein complex, 弁 (Japanese, Proactivator polypeptide, Felis catus, Zealand Rabbits, DmelCG1849, igaad, strontium formate, l(3)84Ab, PRP-3|PRP-4, strontium salt, Carnitine acetyltransferase, Peptide, group, Rabbits, LC/MS/MS, MODIFIER OF SNC1, natural protein, PKBS, Period, p230, 16-Dioxa-8, water, Protein, deoxyribonucleic photolyase activity, I2PP2A, New Zealand, TFIID, Dyrk1, Sad, Cat, CAT, buccal cavity, ACETONITRILE, tandem MS, cyanomethane, optidase activity, NZW Rabbit, Cas-1, c-KIT, PRP-1|PRP-2, INI, with urinary tract Abnormality and cryptorchidism, TAF[[II]]230, Salivary acidic proline-rich phosphoprotein 3|4, photolyase activity, CC1, Rds3, TAF[II]250, l(1)19Ea, sad, cat, NZW Rabbits, sample population, chromic formate, Protein Gene Products, P235, dSET/TAF-Ibeta, c-kit, 2610030F17Rik, DmelCG17603, Domestic Rabbit, Ion, Cat01, concentration, New Zealand Rabbit, 7S Gamma Globulin, calcium salt, Allerglobuline, Sulfatide|GM1 activator, Peptid, assay, AA407739, CG32810, Glucosylceramidase activator, TAF11110007B08Rik, HTRX1, l(1)G0251, l(1)16-94, Neoplasms, Colony-Forming Units, Progenitor Cell, Pancreas Cancer, Gene, MLL|GAS7, pancreas, protein, protein-containing complex, Pancreas Cancers, MLL1A, CFAP89, Pancreatic Neoplasm, Cxxc7, protein polypeptide chains, Ca tail of pancreas, WDS, Wds, Ca head of pancreas, SF3b14b, polypeptide chain, Pancreatic Cancer, Ac2-246, Gene Products, big-3, Mother Cells, Pancreatic Acinar, protein aggregate, 2410008O07Rik, Progenitor, Pancreatic Carcinomas, BIG-3, Pancreatic Carcinoma, Acinar Carcinoma, AA960360, ALL-1, inhibiteur, Mother, Big-3, proteins, Pancreatic Cancers, Mll1, MLL1, 6430520K01, inhibidor, DNA Dependent RNA Polymerase II, associated, Pancreatic Acinar Carcinomas, EG:BACR25B3.7, pancreatic tumour, pancreas neoplasm, Cancer, inhibitors, Carcinoma, swd3, Colony Forming Unit, DmelCG17437, protein complex, Mll, MLL, HRX, malignant neoplasm of body of pancreas, Progenitor Cells, Proteins, pancreatic neoplasm, zw-8, familial, inhibitor, Mother., WDR5, zw8, MLL/GAS7, Pancreas Neoplasm, Cell, wdr5, native protein, Colony-Forming Unit, natural protein, Stem Cell, Protein, Neoplasm, pancreatic carcinoma, Pancreatic, Cancer of the Pancreas, Carcinomas, Mother Cell, TET1-MLL, malignant neoplasm of tail of pancreas, AA408785, pancreatic tumor, INI, SAP14b, SF3B7, Cancer of Pancreas, l(1)3Ad, RNA Pol II, malignant neoplasm of head of pancreas, CXXC7, Stem, All1, WDSTS, Rds3, Colony Forming Units, Cancers, xwdr5, mKIAA4050, Pancreas, Pancreatic Acinar Carcinoma, Protein Gene Products, Big, Gene Proteins, Ca body of pancreas, l(1)zw8, Cells, TRX1, RNA Polymerase B, SWD3, DNA-Dependent RNA Polymerase II, PNCA, Pancreas Neoplasms, bK223H9.2, CG17437, Acinar CarcinomasDmelCG2342, DmelCG2341, DmelCG1252, E 920, delta, determination, leg, Somatomedin-C, protein, contrasted, L-(+)-glutamine, UCRBP, l(1)AA33, peptide, Polypeptides, YIN-YANG-1, L-Isomer Methionine, protein polypeptide chains, L-Glutaminsaeure-5-amid, Methionine, peptido, 0926/11, CG1331, 1, 2, L-2-aminoglutaramic acid, 2-amino-3-mercaptopropanoic acid, Cystein, Software Engineering, protein aggregate, WMS, Computer Program, C79691, DL-Asparagine, C, D, asparagina, DELTA, Man (Taxonomy), peptides, cisteina, M, N, C1, L-Asparagine, Open, D-Glutamine, Q, SF, Computer Programs and Programming, Kitl, proteins, DmelCcp84Af, Y, DmelCcp84Ag, Mast cell growth factor, ASN, Asn, EG:196F3.2, Lccp, DELTA1, DmelCcp84Ab, DmelCcp84Aa, DmelCcp84Ad, l(1)B2/13.1, RUN, Run, ppm, CCA3, Mechano growth factor, delta D1, PDN-21, Soluble KIT ligand, Delta, Half Cystine, Sl, GPHYSD2, Racemethionine, CG3619, SGS, Glutamin, IGF-I, DmelCG1331, BcDNA:RE04513, l(1)LB9, DL, 1053/14, Zinc Cysteinate, Modern, 2-Amino-4-(methylthio)butyric acid, IBP1, Cys, Source Softwares, AA33, sKITLG, Software Tools, ACMICD, Programs, Program, Computer Applications, DL1, NF-E1, Algorithm, Computer Applications Software, Computer Applications Softwares, PCC, Methionin, CG2341, CG1252, Hmet, Softwares, CG2342, CG14784, Igf-1, (2R)-2-amino-3-sulfanylpropanoic acid, L Glutamine, CG14783, parent ion, Hgln, SHEP7, Software Applications, mast cell growth factor, MS/MS, Source Software, DmelCG3619, Stem cell factor, common, MASCOT, L-Cysteine, MASS, 2-amino-3-carbamoylpropanoic acid, STAT5, (S)-2, 1304/03, beta Trypsin, human, CT12133, Crap, L-Cystein, L-glutamic acid gamma-amide, Kitlg, Applications, KL-1, precursor ion, Biocatalyst, MARP, Polypeptide, DmelCG32810, l(3)92Ab, Liquimeth, Gb, Proteomes, humans, Computer Software Applications, l(3)j8C3, CARP, CG1849, GLUTAMINE, Clo, human being, Cysteine Hydrochloride, 2-amino-4-(methylsulfanyl)butanoic acid, AW549739, Slf, SLF, Biocatalysts, 5-diamino-5-oxopentanoic acid, anon-WO0118547.269, L-Zystein, L Isomer, FBN, Levoglutamide, Hasp, Gene, FPH2, precursor, Computer, (2S)-2-amino-4-carbamoylbutanoic acid, protein-containing complex, Human, Glutaminsaeure-5-amid, Carp, CACA, Homo sapiens, polypeptide chain, ECTOL1, Gene Products, L-Methionine, Half-Cystine, 2-Aminoglutaramic acid, Man, Pedameth, Application, BG:DS00004.7, Open Source Softwares, BG:DS00004.6, BG:DS00004.1, CG2360, 1119/09, MS2, BG:DS00004.4, L Cysteine, (2S)-2, Software Application, Runt, E-920, BG:DS00004.2, INO80S, beta-Trypsin, Open Source Software, Sciences, Calcitonin, Hcys, CTRCT4, man, Probabilities, Computer Software Application, OCTD, Asparagin, mKIAA0989, Con, Enzyme, 2-amino-4-(methylthio)butanoic acid, 10^[-6], Tools, CYSTEINE, LMPY, Katacalcin, blz, FREE CYSTEINE, dmDelta, L-Glutamine, peptidos, (2R)-2-amino-3-mercaptopropanoic acid, metionina, LB5, Applications Software, Open Source, Computer Software, l(3)05151, DL-Methionine, protein complex, Proteins, 1440/11, DmelCG1849, total expressed protein, L-2-Aminoglutaramic acid, Rnt, L-Isomer, Peptide, Tool, lLB5, polypeptide, Software Tool, native protein, natural protein, cry-g-D, Protein, 0495/20, chemical analysis, Glutamic acid 5-amide, MFS1, L-Glutamin, Software, tandem MS, Zystein, Data Base, WMS2, Met, CRYG4, MARP1, PRSS, Glutamic acid amide, 2-amino-3-sulfanylpropanoic acid, 1423/11, Calcitonin carboxyl-terminal peptide, Engineering, cc3, Tripcellim, cc2, cc5, L-2-Amino-3-mercaptopropionic acid, l(1)19Ea, Alrp, cc7, (R)-2-amino-3-mercaptopropanoic acid, E(ls)2, cc8, 4-diamino-4-oxobutanoic acid, 2-Amino-3-mercaptopropionic acid, DmelCG2360, Protein Gene Products, P235, Computer Programs, Trypure, Gene Proteins, 2-amino-4-carbamoylbutanoic acid, Applications Softwares, D Glutamine, 1485/04, MGF, Mgf, Modern Man, glutamic acid gamma-amide, c-Kit ligand, SSKS, alpha-amino-gamma-methylmercaptobutyric acid, Ccp, CCP, E920, Peptid, assay, SCF, variable, CG32810, Peptide.falseTargeting an RNA polymerase II-associated PHF5A protein subcomplex with a KMT2A-WDR5 inhibitor impairs self-renewal and tumorigenicity of pancreatic cancer stem cellsPancreatic cancer (PC) remains one of the most aggressive and life-threatening malignancies known for its notorious resistance to chemotherapy. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which are evolutionary fitter than other tumor cells to evade the cytotoxic effects of chemotherapy. Those cells are crucial for tumor relapse as they possess ‘stem cell-like’ features of self-renewal and differentiation. However, what molecular mechanisms maintain the unique characteristics of PCSCs are poorly understood. Here, we identified an RNA polymerase II-associated PHF5A-PHF14-HMG20A-RAI1-KMT2A transcriptional subcomplex, which regulates the stemness characteristics and tumorigenicity of PCSCs through epigenetic control of gene expression. Targeting the protein subcomplex with a KMT2A-WDR5 inhibitor attenuated the self-renewal and in vivo tumorigenicity of PCSCs, thus offering a novel anti-PCSCs targeting strategy for enhancing the efficiency of chemotherapy which is likely to translate into durable clinical responses in PC patients.2023-08-232022-11-26PXD038378NEWT:6945NEWT:3555NEWT:2NEWT:157546NEWT:35554NEWT:38942NEWT:307972NEWT:32046NEWT:544496NEWT:2042546NEWT:45351NEWT:43179NEWT:4513NEWT:376741NEWT:55153NCBITaxon:10407NEWT:1736309NEWT:1211601NEWT:876138NEWT:237561NEWT:5833NEWT:6928NEWT:10036NEWT:36745NEWT:1351NEWT:1438992NEWT:2649997NEWT:272563NEWT:224326NCBITaxon:79857NEWT:95648NEWT:3885NEWT:3888NEWT:1589NEWT:135622NEWT:6915NEWT:3649NEWT:101510NEWT:3880NEWT:272559NEWT:3641NEWT:383379NEWT:10029NEWT:1000589NEWT:85962NEWT:317447NEWT:7955NEWT:7959NEWT:2261NEWT:31156NEWT:4565NEWT:1264690NEWT:515619NEWT:192875NEWT:34305NEWT:59729NCBITaxon:183674NEWT:224308NEWT:626528NEWT:139927NEWT:4558NEWT:209285NEWT:1283NEWT:931281NEWT:4550NEWT:1000561NEWT:197NCBITaxon:79824NEWT:4787NCBITaxon:4563NEWT:5755NEWT:44689NEWT:3218NEWT:5759NEWT:1736231NEWT:1270NEWT:2242NEWT:4784NEWT:11320NEWT:360106NEWT:287NEWT:10117NEWT:10239NEWT:10116NEWT:1280NEWT:1735272NEWT:83334NEWT:83332NEWT:44685NEWT:317513NEWT:1148NEWT:580240NEWT:294128NEWT:11676NEWT:55571NEWT:100226NEWT:4530NEWT:4896NEWT:75058NEWT:13616NEWT:1094343NEWT:296543NEWT:1773NEWT:1895NEWT:1182590NEWT:935293NEWT:64152NEWT:4924NEWT:749200NEWT:990346NEWT:145953NEWT:257309NEWT:100816NEWT:263NEWT:230741NEWT:52283NEWT:284812NCBITaxon:1313NEWT:43330NEWT:408169NEWT:44544NEWT:4911NEWT:645463NEWT:3702NEWT:129249NEWT:990119NEWT:408172NEWT:408170NEWT:493760NEWT:260710NEWT:257313NEWT:400772NEWT:3708NEWT:128161NEWT:332648NEWT:106592NEWT:536231NEWT:1432138NEWT:10312NEWT:1424507NCBITaxon:1773NEWT:9598NEWT:8030NEWT:1639NEWT:188229NEWT:3818NEWT:480NEWT:4909NEWT:67767NEWT:432359NEWT:46835NEWT:2711NEWT:376686NEWT:95486NEWT:9103NEWT:29159NEWT:10306NCBITaxon:2759NEWT:1233435NEWT:8022NEWT:145943NCBITaxon:4932NEWT:595536NEWT:240906NEWT:593117NEWT:3635NEWT:5811NEWT:235443NEWT:411483NEWT:884019NEWT:198215NEWT:411490NEWT:983964NEWT:169963NEWT:499175NEWT:476272NEWT:3747NEWT:367830NEWT:178616NEWT:410289NEWT:373153NEWT:352472NEWT:360094NEWT:470NEWT:1313NEWT:411469NEWT:84023NCBITaxon:5811NEWT:411464NEWT:411460NEWT:2762NEWT:1174673NEWT:562NEWT:411470NEWT:33952NEWT:2094720NCBITaxon:2697049NEWT:28038NEWT:1423NEWT:4932NEWT:3603NEWT:2759NEWT:3847NEWT:327159NEWT:178876NEWT:327160NEWT:573NEWT:9031NEWT:7091NEWT:241368NEWT:42528NEWT:190802NEWT:9778NEWT:150475NEWT:9417NEWT:7111NEWT:347515NEWT:1216979NEWT:5180NEWT:256737NEWT:115104NEWT:1081927NEWT:1238993NEWT:67825NEWT:185579NEWT:13076NEWT:1249668NEWT:317NEWT:7227NEWT:7469NEWT:885318NEWT:9402NEWT:415540NEWT:4081NEWT:554NEWT:98334NEWT:426428NEWT:7574NEWT:7215NEWT:575412NEWT:29204NEWT:2172103NEWT:507601NCBITaxon:6157NEWT:746360NEWT:6239NEWT:470150NEWT:216257NEWT:9986NEWT:4054NEWT:73239NEWT:226186NEWT:1268063NEWT:8782NEWT:1263854NEWT:435590NEWT:1902NEWT:160488NEWT:28104NCBITaxon:2NEWT:985076NEWT:1215323NEWT:52641NEWT:7038NEWT:6192NEWT:28532NCBITaxon:38727NEWT:2829NEWT:216599NEWT:216595NEWT:243230NEWT:8355NEWT:9685NEWT:7029NEWT:1080772NEWT:1283300NEWT:6183NEWT:6063NEWT:334747NEWT:61235NEWT:6289NEWT:436486NEWT:6287NEWT:300641NEWT:727NEWT:9796NEWT:725NEWT:170187NEWT:260707NCBITaxon:6191NEWT:1836NEWT:185431NEWT:29760NEWT:260704NEWT:703612NEWT:260705NEWT:80863NEWT:2697049NCBITaxon:6073NEWT:884204NEWT:6279NEWT:1123869NEWT:9544NEWT:7370NEWT:83906NEWT:607699NEWT:6282NEWT:208964NEWT:1134506NEWT:575584NEWT:38783NEWT:8727NEWT:4006NEWT:8726NEWT:6426NEWT:6669NEWT:10090NEWT:4120NEWT:51515NEWT:5693NEWT:8724NEWT:51511NEWT:92867NEWT:8723NEWT:5334NEWT:37334NEWT:382352NCBITaxon:10359NEWT:242619NEWT:632957NEWT:373995NEWT:5689NEWT:544404NEWT:9925NEWT:8839NEWT:4232NEWT:2758385NEWT:4113NEWT:837NEWT:11298NEWT:171101NEWT:714NEWT:421932NEWT:196627NEWT:5691NEWT:48479NEWT:627025NEWT:1097677NEWT:61674NEWT:1117957NEWT:9913NEWT:4100NEWT:1076NEWT:6763NEWT:803NEWT:29722NEWT:380394NEWT:1692259NEWT:180066NEWT:135588NEWT:1843183NEWT:58002NEWT:326423NEWT:4577NEWT:1416333NEWT:5664NEWT:2157NEWT:418985NEWT:146479NEWT:1911079NEWT:264203NEWT:1480154NEWT:1274414NEWT:27606NEWT:59202NEWT:9975NEWT:9612NEWT:38865NEWT:51953NEWT:3197NEWT:9615NEWT:10299NEWT:860688NEWT:36329NEWT:1147787NCBITaxon:3044782NEWT:72407NEWT:349741NEWT:9605NEWT:9606NEWT:157295NEWT:641501NEWT:7668NEWT:915099NEWT:74940NEWT:9721NEWT:137221NEWT:1450511NEWT:1143193NEWT:411901NEWT:9838NEWT:105884NCBITaxon:9615NEWT:58334NEWT:1193501NEWT:3055NEWT:6326NEWT:6689NEWT:5476NEWT:1274432NEWT:1274426NEWT:70448NEWT:9825NEWT:1274423NEWT:393765NEWT:698936NEWT:39946NEWT:9823NEWT:9940NEWT:521001NEWT:39947NEWT:1274420NEWT:5784580000-0002-8155-5272