Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006455.dat-pride.xml-merged.xml.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_PP_E6.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_TP_F3.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_TP_F8.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_PP_E10.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_PP_E9.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_TP_F2.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_TP_F7.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_PP_E5.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_TP_F1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_PP_E11.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_PP_E4.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/QE2_Fevzi_TP_F6.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006455.dat-pride.xml-merged.pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006455.dat-pride.xml-merged.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006456.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006465.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006460.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006464.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006455.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006472.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006463.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006467.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006476.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006471.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006462.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD008276/F006458.datprimaryOK200p.cutillas@qmul.ac.ukPedro Casado-IzquierdoMass SpectrometryShotgun proteomicsNot availableFakMetabolismFibroblasthttp://www.ebi.ac.uk/pride/archive/projects/PXD008276Primary CellEpithelial CellFibroblastFor proteomics and phosphoproteomics studies, cell lysis and trypsin digestion was performed as previously described30. Phosphopeptides were enriched using TiO2 (GL Sciences)30. For phosphoproteomics, dried peptide pellets were resuspended in 9 µL of reconstitution buffer (20 fmol/µL enolase digest in 3% ACN, 0.1% TFA) and 5.0 µL were loaded onto an LC-MS/MS system consisting of a Dionex UltiMate 3000 RSLC directly coupled to an Orbitrap Q-Exactive Plus mass spectrometer (Thermo Fisher Scientific). For proteomics, pellets were resuspended in reconstitution buffer (0.5 µg/µL) and 2 µL were injected. The LC system used mobile phases A (3% ACN: 0.1% FA) and B (100% ACN; 0.1% FA). Peptides were trapped in a µ-pre-column and separated in a nanoflow analytical column. The following parameters were used: 3% to 28% B gradient for 120 min and a flow rate of 0.25 µL/min. Eluting peptides were analysed in a QExactive Plus system with scan survey spectra (m/z 375-1,500) was followed by, datadependent acquisition of the 15 most intense ions were selected for HCD (higher energy collisional dissociation) and MS/MS scanning (200-2,000 m/z) with a resolution of 17,500 FWHM. A 30 s dynamic exclusion period was enabled with 10 ppm mass window. Peptide identification and quantification was carried out from the MS/MS andPrideNot availablephosphorylated residueiodoacetamide derivatized residuedeaminated residuemonohydroxylated residueMS data using the Mascot search engine as described before. Kinase substrate enrichment analysis (KSEA) was carried out by grouping peptides into substrate sets known to be phosphorylated by a specific kinase23. Gene ontology enrichment analysis of proteins differentially phosphorylated between conditions (at p < 0.05) was carried out using the hypergeometric test.ProteomicsPedro R. CutillasQ ExactiveCentre for Haemato-oncology, Barts Cancer Institute, Queen Mary University of London, London, EC1M6BQ, UKCOMPLETEMus Musculus (mouse)p.m.casado-izquierdo@qmul.ac.ukNot availableBiomedicalCell SignallingUnited Kingdom10.6019/PXD008276liquid chromatography tandem mass spectroscopy, CPD photolyase activity, PhrB photolyase activity, ion, Peptidomics, Effects, FBN, ACINUS, photoreactivating enzyme activity, pigmented epithelium, thomson, body system, deoxyribodipyrimidine photolyase activity, CG7826, Long Term, LC-MS-MS, stratum pigmentosum retinae, Buffer, mass-to-charge ratio, peptide, period, Polypeptides, ClvPrd, peptido, BANF, ECTOL1, LC-MSMS, CG7835, CG42273, system, 3, Min, stratum pigmentosa retinae, NUP96, outer pigmented layer of retina, epithelium, Separated, Effect, WMS, DmelCG42273, Divorced, anatomical systems, MOS3, C79325, LCMSMS, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, peptides, Acinus, PRECOCIOUS, Longterm, iones, 2610036I19Rik, beta-Trypsin, 2610510L13Rik, pigmented retina, F23A5.3, min, Sciences, mAPC, Divorces, Long-Term, ions, SCAN, DNA cyclobutane dipyrimidine photolyase activity, SUPPRESSOR OF AUXIN RESISTANCE 3, acinusL, AI047805, OCTD, fSAP152, pigment epithelium of retina, column, 10^[-6], acinusS, 2-phosphoglycerate dehydratase, ACN, ppm, Acn, pigmented retina epithelium, peptidos, Long-Term Effect, GPHYSD2, Long-Term Effects, F23A5_3, SGS, LC-MS2, PRE, DYRK1, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, LC-MS/MS, 2-phospho-D-glycerate hydro-lyase, Dmel_CG7826, Longterm Effect, Th, pigmented retinal epithelium, buffer, Peptide, mKIAA0670, ACMICD, polypeptide, stratum pigmentosum (retina), LC/MS/MS, MODIFIER OF SNC1, Phosphopeptide, HCD, retinal pigment, Dm1, Ionen, Long Term Effects, deoxyribonucleic photolyase activity, dipyrimidine photolyase (photosensitive), MFS1, Dyrk1, connected anatomical system, FWHM, retinal pigment layer, Dmel_CG7835, WMS2, Mnb, MNB, AU020952, Separation, RPE, photolyase activity, retinal pigmented epithelium, Separations, CC1, Tripcellim, fmol, MASS, AW124434, beta Trypsin, retinal pigment epithelium, Longterm Effects, p. pigmentosa retinae, ME-IV, organ system, Trypure, phr A photolyase activity, eno, DNA-photoreactivating enzyme, Ion, liquid chromatography-tandem mass spectroscopy, SSKS, liquid chromatography tandem mass spectrometry, Peptid, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Polypeptide, SCH, time, Peptide.Gene., data, Gene Ontology Projects, determination, AW549739, protein complex, Proteins, Gene, Search, protein, protein-containing complex, Phosphotransferases, Peptide, Gene Ontology Project, Engine, Gene Ontology, polypeptide, peptide, Polypeptides, protein polypeptide chains, peptido, native protein, natural protein, polypeptide chain, chemical analysis, Protein, Gene Products, Project, Ontology Projects, Kinase, protein aggregate, Phosphotransferase, C79691, Ontology Project, Gene Ontologies, Search Engines, Transphosphorylases, Ontology, Ontologies, peptides, Projects, Kinases, MASCOT, proteins, Transphosphorylase, Lccp, Protein Gene Products, mKIAA0989, Gene Proteins, Peptid, peptidos, assay, Polypeptide, ATP Phosphotransferases, ATPacf1, malignant Growth, MMTV, SUS1, exocrine cancer, Laboratory, vcfs, Glukose, Metabolic Concepts, VCFS, Embden-Meyerhof, growth and development, Tumor, House Mouse, dgcr, dorv, 5730420M11Rik, dmTAF[[II]]230, Tumor-Associated Fibroblasts, Fak56D, tumour of pancreas, DGCR, Dextrose, DORV, TGA, DGS, DFak, DFAK, cancer of the breast, Kinase, Metabolism Concept, Fs(3)Hor, GROa, Progression, BC, SET, TFIID TAF250, cel, catabolism, ACF/CHRAC, cell process disease, tumor disease, phosphatase 2A inhibitor I2PP2A, P, Cancer-Associated Fibroblast, ACF1, Pathways, metabolic process resulting in cell growth, glucose catabolism, Pancreatic Cancers, NTef2, CA, DmelCG4299, glucose, set, ACF, Acf, decreased, HMUDG, cancer of breast, Dfak, Tumor Associated Fibroblasts, stage, ATP Phosphotransferases, fak56, single organism signaling, Tumors, malignancy, dTAF[[II]]230, Pathway, pancreatic cancer (not islets), metabolism resulting in cell growth, malignant neoplasm of body of pancreas, familial, TAF200, anaerobic glycolysis, cancer of the pancreas, malignant pancreatic neoplasm, Fibroblasts, Embden-Meyerhof-Parnas, not genetically inherited, tumours, Fs(3)Sz11, Embden-Meyerhof-Parnas Pathway, HSP, tumor of the pancreas, secretion, pancreatic carcinoma, PANCREATIC NEOPL, Pancreatic, (alpha-D)-Isomer, Strumpell-Lorrain disease, D-Glucose, Cancer of Pancreas, HLA-DR-associated protein II, Caspase-14 subunit p10, neoplasm of the pancreas, DI-2, malignant neoplasm of head of pancreas, xtbx1, I-2Dm, Swiss Mouse, Caspase-14 subunit p19, inhibitor of granzyme A-activated DNase, SHORT INTEGUMENTS 1, pancreas carcinoma, Pancreas, CHRAC-175, human, I-2PP1, tumour disease, gro, tumour of the pancreas, glycolysis, TAF-IBETA, malignant neoplasm of the pancreas, Taf250, Ca body of pancreas, breast cancer, CG2684, Mouse, TAF-Ibeta, other neoplasm, Glucose Monohydrate, carcinoma of the breast, cancer, Embden-Meyerhof Pathways, Fibroblast, TAF230, 3.4.22.-, UNG3, advanced, NEOPL PANCREATIC, Glucose, Peptidomics, tbx1c, Processes, Neoplasms, cell type cancer, developmental stage, Pancreas Cancer, P/CAF, mini-ICE, Angiogeneses, pancreas, familial spastic paraplegia, cthm, Scyb1, Metabolic Processes, familial spastic paraparesis, Pancreas Cancers, NEOPL, FSP, Fsp, Cancer Associated Fibroblast, CTHM, SUSPENSOR 1, Pancreatic Cancer, Mus musculus domesticus, vascular element, neoplasm, malignant tumour, dTAF[[II]]250, Clinical, SCYB1, cell, MGSA, Metabolic Concept, 2pp2a, tumour, KC, man, P|CAF, CG10574, focal contact, dTAF250, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), 2PP2A, Clinical Course, blood vessel formation from pre-existing blood vessels, dSET, dSet, Cancer-Associated, constitutitional genetic, Anhydrous, Neoplastic Growth, PCAF, Cancer, pancreatic adenocarcinoma, cafs, degradation, SPG, carcinoma of breast, pancreatic neoplasm, tbx1, BG:DS00004.13, Fak56, Pancreas Neoplasm, Cell, dTAF230, Concept, neoplastic growth, MT, Cytokine, I-2PP2A, Mgsa, T25K16_4, dACF, chemical analysis, Dm I-2, Neoplasm, TAF[[II]]250/230, CAFS, glucose breakdown, metabolism, region of vascular tree organ, Mtvr2, Metabolic Phenomenon, Taf[[II]]250, malignant neoplasm of tail of pancreas, multicellular organism metabolic process, pancreatic tumor, primary cancer, Cancer Associated, underdeveloped, postnatal growth, pancreatic cancer, exocrine pancreas carcinoma, House Mice, Cancers, Lds, disease of cellular proliferation, malignant tumor, signalling, signalling process, CATCH22, spastic paraplegia, vascular tree organ region, malignant pancreas neoplasm, Pancreas Neoplasms, hereditary, NEOPLASMS BENIGN, Neoplasia, dCHRAC, breast, Anabolism, biochemical pathways, French settlement disease, IPP2A2, Metabolic Process, Breasts, Strümpell-Lorrain disease, determination, EMBRYO DEFECTIVE 60, neoplasia, Mus domesticus, postnatal development, Tumor-Associated, CT28129, Tumor-Associated Fibroblast, Monohydrate, CASP-14, Imaging, (DL)-Isomer, Anabolism., Embden Meyerhof Parnas Pathway, Pancreatic Neoplasm, CARPEL FACTORY, Ca tail of pancreas, Ca head of pancreas, ASU1, Concepts, Embden-Meyerhof Pathway, Phenomenon, Dfak56, present in fewer numbers in organism, CG10023, pancreas tumour, adhesion plaque, neoplasm of pancreas, hemi-adherens junction, DmelCG2684, MGSA-a, TAF-I, neoplasm (disease), Exocrine pancreas carcinoma, hypoplasia, Swiss Mice, DmFAK, tumor of pancreas, DL-glucose, SIN1, genetic, IGAAD, EMBRYO DEFECTIVE 76, DmelCG10574, malignant neoplasm, carcinoma of the pancreas, signaling process, HAJ, Exacerbation, biotransformation, Cancer Associated Fibroblasts, tumor, associated, Catabolism, ATP, pancreatic tumour, pancreas neoplasm, mamma, pancreas tumor, phapii, Fadk, Process, malignant neoplasm of pancreas, glucose degradation, mouse, Disease Exacerbation, StF-IT-1, late, neoplastic disease, carcinoma of pancreas (disorder), TAFII-250, D330035F22Rik, TAF250/230, FADK, TAFII250, BC020531, Mini-ICE, organ system cancer, precocious, NOS, breast carcinoma, Cancer of the Pancreas, CHRAC, 1110021A21Rik, Mus musculus, Transphosphorylases, DmelCG10023, exocrine pancreatic carcinoma, Acf-1, growth pattern, mice, non-developmental growth, CG4299, CG17603, MICE, TAF[[II]], Embden-Meyerhof pathway, early, domesticus, loss of, cancer of pancreas, DICER-LIKE 1, Patient, D Glucose, SR3-5, Horka, FAK, Fs(3)Horka, inherited genetic, PNCA, i2pp2a, gluco-hexose, mammary region, d230, biological signaling, human being, EMB76, NAP-3, fak, dTAFII250, CG1966, pancreas cancer, EfW1, PHAPII, p170/p185, AI666765, EMB60, reduced, template-activating factor I, dmTAF1, House, Taf230, subnumerary, Metabolism, Clinical Progression, mKIAA4203, DmF2, tiny, VCF, Metabolism Phenomena, Mice, Phosphotransferase, TAF250, PANCREAS NEOPL, lod, carcinoma of pancreas, Taf200, FDG, hereditary spastic paraparesis, Swiss, ipp2a2, mammary part of chest, Taf1p, mammary carcinoma, vas sanguineum, Transphosphorylase, decreased number, connecting hemi-adherens junction, FAK1, taf-ibeta, N51, Clients, TAF, modifed Embden-Meyerhof pathway, ATDCL1, small, Disease, data, TAF[[II]]250, adequate, pp125FAK, Embden Meyerhof Pathway, (beta-D)-Isomer, malignant, igaad, l(3)84Ab, pancreas neoplasm (disease), Client, Phosphotransferases, p125FAK, Metabolic Phenomena, development, Metabolism Concepts, Phosphopeptide, FRNK, CAF, Mus, p230, DmelCG1966, malignant neoplasm (disease), Phenomena, I2PP2A, TFIID, RCB0186, T25K16.4, TAF[[II]]230, biodegradation, Metabolic, Kinases, Gro1, GRO1, AW455831, carcinoma of exocrine pancreas, TAF[II]250, dicer-like 1, Embden-Meyerhof-Parnas pathway, Pancreatic Neoplasms, DFak56, PPP1R71, Anhydrous Dextrose, Laboratory Mice, TBX1C, dSET/TAF-Ibeta, single-organism metabolic process, 2610030F17Rik, DmelCG17603, DEL, malignant neoplastic disease, assay, AA407739, growth, Laboratory Mouse, ABNORMAL SUSPENSOR 1, Intrinsic, TAF1, Glcbiochemical pathways, malignant Growth, d230, Metabolic Process, Processes, cell type cancer, fak, Metabolic Concepts, CT28129, dTAFII250, Metabolic Processes, Anabolism., EfW1, dmTAF[[II]]230, Fak56D, dmTAF1, Taf230, Metabolism, Concepts, DFak, DFAK, mKIAA4203, Metabolism Concept, Dfak56, Phenomenon, neoplasm, Metabolism Phenomena, malignant tumour, CG10023, TAF250, Taf200, dTAF[[II]]250, TFIID TAF250, cel, cell, catabolism, neoplasm (disease), Metabolic Concept, Taf1p, metabolic process resulting in cell growth, DmFAK, primary dermal fibroblast, CA, FAK1, dTAF250, malignant neoplasm, Dfak, biotransformation, associated, TAF, fak56, Catabolism, Fadk, malignancy, dTAF[[II]]230, TAF[[II]]250, pp125FAK, mouse embryonic fibroblast, degradation, Process, malignant, metabolism resulting in cell growth, TAF200, l(3)84Ab, BG:DS00004.13, Fak56, TAFII-250, TAF250/230, p125FAK, Cell, dTAF230, Concept, Metabolic Phenomena, FADK, Metabolism Concepts, TAFII250, MT, FRNK, p230, malignant neoplasm (disease), organ system cancer, Phenomena, TAF[[II]]250/230, TFIID, secretion, metabolism, Metabolic Phenomenon, Taf[[II]]250, multicellular organism metabolic process, primary cancer, TAF[[II]]230, DmelCG10023, biodegradation, Metabolic, TAF[II]250, CG17603, TAF[[II]], malignant tumor, DFak56, PPP1R71, single-organism metabolic process, DmelCG17603, Taf250, malignant neoplastic disease, SR3-5, FAK, cancer, Fibroblast, TAF230, TAF1falseCancer Associated Fibroblast-FAK regulates malignant cell metabolismBreast and pancreatic cancers are characterised by profound metabolic changes1,2. Until recently, these changes have been ascribed to their intrinsic genetic profiles2-4. However, the contribution of cancer-associated fibroblasts (CAFs) to cell metabolism has not been fully investigated5. Here, we provide clinical evidence that reduction in stromal Focal Adhesion Kinase (FAK) correlates with reduced overall survival in human breast and pancreatic cancer patients. To model this, we developed FSP-Cre+;FAKfl/fl mice where FAK was deleted in a subpopulation of CAFs. We establish that loss of CAF-FAK is sufficient to enhance tumour growth without affecting desmoplasia in orthotopically injected breast and pancreatic carcinomas. Additionally, deletion of CAF-FAK enhances disease progression in the MMTV-PyMT spontaneous model of breast cancer. Furthermore, despite this pro-tumourigenic effect, a significant reduction in tumour angiogenesis was observed in late-stage tumours, but not early-stage, size-matched tumours in FSP-Cre+;FAKfl/fl mice. This indicates that loss of CAF-FAK is sufficient to reduce malignant cell dependency on blood vessel support suggesting acquired metabolic alterations in cancer cells. Indeed, 18F-FDG-PET imaging and glucose flux analysis revealed enhanced glucose catabolism in early-stage, size-matched tumours in FSP-Cre+;FAKfl/fl mice in vivo. Mechanistically, we demonstrate that conditioned medium from FAK-null CAFs enhances glycolysis and glycolytic capacity in malignant cells. Proteomics and phosphoproteomics analysis reveal enriched cytokine-mediated signalling pathways in FAK-null CAFs and subsequent enrichment of associated phosphopeptides in malignant cells, respectively. Overall, our data uncover a novel mechanism by which cytokines, regulated by CAF-FAK, can promote cancer growth and progression, and identify a new set of CAF-derived targets to interfere with cancer metabolism.2020-02-182017-11-23PXD008276280655164609918049829535851114528421880905811363336351524260119832758385NCBITaxon:128068888561896111430118726355557114526236493461327467073853883641135461582158236889547627211232944222911809923233654583334607925193659143205971293865581914932637371250232NCBITaxon:1272111957748186614885843451358672217554374081691804542668344530586126683514982250581496367458554528113208147956410039237514636942049433208964208963445974137979128384400667935293671521659940483216597216595455013152826930421659156271616968332183217292042779447623764543172030949801975255569781439843948840479NCBITaxon:2157525338551531051067439899037122857759515205968762311210884555588845587077918178081736309431794571698936160488409859NCBITaxon:3716210478267940150590714836432042106132049138169363035554320466326334565453511025411103217459216129410026420369456941016763410210761277351131658239254727933428146135843017463345774449167547604893212873567568403019172651813019411192943936711041131023932025559863258278839659104759347495165299835525663175854310243260866310245980875741755518320196447145268045796190832331156114155421932555217634123598755529NCBITaxon:47518502547611361574146547718006655648433767729976798251021699823897641373511557444474153NCBITaxon:505578996984410003646534933414754801946751299114359741276473137086326547876569835322159983819201110348198524794640986099586766859919157295137221171101107687834974198601488406334249235985988655974649987039202111072943311711397215987419085037117082841823502414511391902197822474636046147123743759392532566489050794526591972211915853101774208588596NCBITaxon:61575052102830798951105198997237505957613172000263419610264940772275689964975157244NCBITaxon:22023717NCBITaxon:1703612857050617476792745062724915961538400524643213686150596866629417347515363291018194301086731018557303963558633149286287132161865368595105135260710185687294296110091416333NCBITaxon:619184023210007348824187878645159812863577553470951451225786260704260705260707658457405416561007133705654195NCBITaxon:3055504457913998781681928752829126806315327341478281055524NCBITaxon:9606469008150251930283672859300852NCBITaxon:5693826883064017946991510151548242838111604193704759272370828167728503515819901195195326738637024924053608862248881756261583558371533376057267119350199808611935021678793711371272407371457125627457903113335503728142433747924910078711082NCBITaxon:961559463318586260799141262200298492670NCBITaxon:1263719281249212528303856838569591169266100658123756127504542666255151978837503600941293497905435247214012576499085151514389923745374744544641524323592887051580595536157932716029385114978633892894535936479437NCBITaxon:68544127542251171590109013416738715895521012966103061296715851584515849376593934327159100226376733889423451287689146479293657616428034216413315992803828035369091089176894621812141080348179392287889295027113117493468192273218903821076012471904007271143114020641198108713554774365814245072295337969820423212422312916321803347087145372091645733157546992877702020603281143193382935508332912922114872526499972830357275507176299707678926837041521405329412816078395639242273775962073220865955516936053307972551811354915974953502611595561432138406072587814144733491949634016143347316461046603815184547448500356709747751240174841833572042746076994688103762014887289093164358500713894649408941442423277422140921157781154756929793244704749906604162103591905158749907312989913112273170187103589915NCBITaxon:3729610360983341130798133679531640729946710340157863033373306383011306413992530642363650595478854698134317103372994044586207340115357111952965261174553111471613386541313166343055213231201798360993512993850573163176426197940115134584457726787286232193348621160791392227983516811961255228149539322116761757312108077213487999948861814084341033519963218496139248820963304393755699286266447NCBITaxon:2697049339862436941103121958832050920290610997586448643249952529724634389427863789426256737863912334355141998349317998686554055343529148654514712454661042986357124679151641358884019373345087718238039129039129529719748693102868899951337310548771251632138985076255470119380625631886571303443516558658862238NCBITaxon:44664946454636493NCBITaxon:110711428006288356491845881087439145943854331116781077854314408043933495346939773821899318226900351281459533996686959541869420030895448697244366206656395453005586233551804264308692200302284812426428150475149910510299102984144523862629035120895571170089306218644193061575584131016538235255772239946360106360104399475444042376102127905688133775182361162296298176771870931281105023824518557966946543186320518240974417394124501288531838891988531911137825591037164735166012615572283313NCBITaxon:1011428450316311985738595233432379560260871213463959842752959526643733432322354431427524224308143361959313345659432741699631122233605201216979525283869728643680121870733474727901040818829760381812498853401884397331274414163958885872520295546480383436912243264081721241935595521281614055920425465519458228860918382712744234081701933298297212744201274426943284139961660187625482964718762474801199150956481882297254314801541204551384738481882945190695116633603648498505693101510528353528352693735294540520297222585941097677812310061911079322710279434472568484793870333849917226175610946161435120325812051365218505235259447320549373474466449917558258038804333012067811220260499108061246196246197320637522991867051186705750906812193879118794739800718680157230746835741258117571508476918388580329031388869152167786721273997844597247512951398704351262469692812397713333995103430481381781821981318826821080228156100547629265716329571922221979116938197912124714854513283882813952949145954161934139036312041623264460711210411706127443210859566941283166694369455972941065810584133087947844751741508082065423174471270281411194669145458695379329201019812646904106611457551392511408157697316062121331238391128312821280339522811010832825253531528512811235315349825741948147875362314241013567429510524261914548111506212945912928299633941597531211705193516309800697810369018853225660173654856615664162425103695118702348334821187056386322261861299250164686068851262321721956581010284283865671713604160235870015048022160100293578613252911187002157641809699756655666452467223926633666336721751117645592321870933114767468NCBITaxon:40559235909322646523652621263374982178707498216347256569156925693872249821165448720569734507699300166690510894491089448NCBITaxon:2759661410NCBITaxon:4932653587155689520710894441000589655087322875351352481263730069303987251211776872687238724872965498727242231305544177257845415814191988224454461174673104105446899601677674468587529600NCBITaxon:5811118226370824855784578458194439158059656636164034624136810893161001428099612NCBITaxon:548681NCBITaxon:58205464143077522836373791966272905896059606875944670875622708626659649604335483309029829387834810626756726756643061512793654319474704721917016108961587827573640782112931457075298352061892577712850248048541898548771587796273002515630415286964696439644491146247274612874601134506963852638526393024095264110909467469416348112386935231NCBITaxon:5659951195623305917365822573132697969903461344346360644042134511249515109760616125732924620096692729422729435133896858355968912801796811186961678078118694143618311869817194759321718118691443906NCBITaxon:102981257118387271566338404330618596948364190802703847664257310568708618218678661833568851350NCBITaxon:7803906NCBITaxon:1502451516702982076211586121845193079209285201319747078529507619212638543915383379NCBITaxon:10239NCBITaxon:7141736130957054704483006417515859238159084128108406972282334575412NCBITaxon:1024528104NCBITaxon:102433920174810977970671356225833136185509924286706527796583342409069102631034809NCBITaxon:6312406741307670707074876138108049267294747276891781212671928532177384645177217743710490561534811992251215323957676901472664709131704720269713038596285963411476130913081263871212035332648373153214693383234114795837013141313493760833341311833335704711149703965539728333210184183331214687455045749200153009107662041149028014851750130373983NCBITaxon:1155239881399274356235931179286683906119459916032932853422999810336578618533658457428316273121536024271831627713519948875058NCBITaxon:104073162752427155027791679718134913062745027802915954126443239291586600255702127211355886755122965879309452031241051519284343581539858015626981182590456099069027256027256335442284109286757227901NCBITaxon:5796537457574011233523562355522221045775126216131091515429310136413962242139213901857323271489623074116402784896160106757445802402512296833529441393665814036657625763206672400540296543NCBITaxon:1170928231772981843183443226224657554992295757575928459370667143673344424035318492231121054211527639109697622611117957529818184319229438152764098662652810442179626782531751327804565050176946NCBITaxon:1313171250389427955880119873251979596214114082241408223264561421971014122851867631854315207677376777421926129454458057041744726724042649329NCBITaxon:1773208893208895207559101176645531523166336745101161328426265872139269635889542301951581988391943661233681449822491155438264131033799866694006884542157535311510429831546891112985935625323266046913616510561214916523897633631681214915970412630821328881885513613NCBITaxon:1865381889083264241916073NCBITaxon:18653662101736604315750393765573111623427306855743680863772166689NCBITaxon:138305959840031972917616089942917030027310523110090405464653224323276056834062178606106453919821597397574419947427577580422777913136623940734076204104411117086937451547922119856119857299204072NCBITaxon:5920165636713926767114501344084408797781074016269941279131478196794408138039452813534038165966861235178616243231243230235612710876717978540964097978893052432776279129249115574840904092409344713512025316376163317831362538865856944155401813397174168709796628773239669202979362899315634301922344713763433872227954866343662821736231259248586110921386388420493211354724847947314473116968111290255161398128481317333672214407721316931555778122152250255183610036NCBITaxon:112668485145494137499010041715916922596345910659213334991065901249615334542NCBITaxon:6622432754427121340112390171658496410289688333124966842528265215810943432652157716019712790857162NCBITaxon:10357NCBITaxon:103581654360507601435590NCBITaxon:1035917072127263418593478341322343802226276261890364196947182528634955983964271191364527262127262327262411771891238993121410246052312189481821314269704940324131808030490314179812483431114778749093238481437113153688918413684174940804980404342714918256136491154373413156713164163159403021009714629772823525675060189519295214505112748492496731460519518766260201580021538186256226912328013603275614231422275119030414505204932275914282664179906914174609111020594082511211143919042762167539131463977851866139077527141061981353008559292148691714511414448340732036962232834959NCBITaxon:11676163434237545136783049525801580236270000-0002-4207-9349