{"database":"MassIVE","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/v03/MSV000085415/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"submitter":["Karen Colwill"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=4acf7c571cae494da025398c933161b4"],"submitter_email":["colwill@lunenfeld.ca"],"sample_protocol":[""],"repository":["MassIVE"],"file_size":["162"],"ptm_modification":["UNIMOD:4 - \"Iodoacetamide derivative.\"","MOD:00046 - \"A protein modification that effectively converts an L-serine residue to O-phospho-L-serine.\"","MOD:00047 - \"A protein modification that effectively converts an L-threonine residue to O-phospho-L-threonine.\"","MOD:00048 - \"A protein modification that effectively converts an L-tyrosine residue to O4'-phospho-L-tyrosine.\"","MOD:00685 - \"A protein modification that effectively converts an L-glutamine residue to L-glutamic acid.\"","MOD:00684 - \"A protein modification that effectively converts an L-asparagine residue to L-aspartic acid.\"","MOD:00719 - \"A protein modification that oxygenates an L-methionine residue to one of the diastereomeric L-methionine sulfoxide residues.\""],"data_protocol":[""],"omics_type":["Proteomics"],"instrument_platform":["TripleTOF 5600"],"species":["Homo Sapiens (ncbitaxon:9606)"],"submitter_affiliation":["LTRI"],"pubmed_abstract":["Epithelial ovarian cancer (EOC) has a unique mode of metastasis, where cells shed from the primary tumour, form aggregates called spheroids to evade anoikis, spread through the peritoneal cavity, and adhere to secondary sites. We previously showed that the master kinase Liver kinase B1 (LKB1) is required for EOC spheroid viability and metastasis. We have identified novel (nua) kinase 1 (NUAK1) as a top candidate LKB1 substrate in EOC cells and spheroids using a multiplex inhibitor beads-mass spectrometry approach. We confirmed that LKB1 maintains NUAK1 phosphorylation and promotes its stabilization. We next investigated NUAK1 function in EOC cells. Ectopic NUAK1-overexpressing EOC cell lines had increased adhesion, whereas the reverse was seen in OVCAR8-<i>NUAK1</i>KO cells. In fact, cells with NUAK1 loss generate spheroids with reduced integrity, leading to increased cell death after long-term culture. Following transcriptome analysis, we identified reduced enrichment for cell interaction gene expression pathways in OVCAR8-<i>NUAK1</i>KO spheroids. In fact, the <i>FN1</i> gene, encoding fibronectin, exhibited a 745-fold decreased expression in <i>NUAK1</i>KO spheroids. Fibronectin expression was induced during native spheroid formation, yet this was completely lost in <i>NUAK1</i>KO spheroids. Co-incubation with soluble fibronectin restored the compact spheroid phenotype to OVCAR8-<i>NUAK1</i>KO cells. In a xenograft model of intraperitoneal metastasis, NUAK1 loss extended survival and reduced fibronectin expression in tumours. Thus, we have identified a new mechanism controlling EOC metastasis, through which LKB1-NUAK1 activity promotes spheroid formation and secondary tumours via fibronectin production."],"pubmed_title":["A novel role for NUAK1 in promoting ovarian cancer metastasis through regulation of fibronectin production in spheroids."],"pubmed_authors":["Fritz Jamie Lee JL, Collins Olga O, Saxena Parima P, Buensuceso Adrian A, Ramos Valdes Yudith Y, Francis Kyle E KE, Brown Kevin R KR, Larsen Brett B, Colwill Karen K, Gingras Anne-Claude AC, Rottapel Robert R, Shepherd Trevor G TG"],"name_synonyms":["Dm IB, bbs15, mind-bomb, Frp, Frizzled-related protein 1, sfrp3, DIP1, DroMIB, MyoIC, LVNC7, Frezzled, l(3)72Db, CG5841, l(3)72CDa, myo61F, frzb-1, fiz, mKIAA1323, fre, frp-3, MYO61F, IB, MYOIB, Dmib, D-mib1, DmIB, Sfrp3, FZRB, xfrzb, MIB, Mib, DmelCG5841, frzb-pen, sFRP-3, FRP-3, dmib1., E430019M12Rik, DIP-1, SFRP3, fritz, fzrb, myo61f, BBS15, FRZB-1, FRZB1, FRZB-PEN, hFIZ, Myo-IB, FRITZ, mindbomb, mib, Frzb-1, CG9155, Fritz, OS1, os1, ZZANK2, C2orf86, DmelCG9155, frezzled, SRFP3, dip-1, Myo1B, frtz, srfp3, D-mib, FrzB-1, frzb1, Mib1, MIB1, FRTZ, ZZZ6, FRE, c2orf86"],"description_synonyms":["bbs15, Frp, Frizzled-related protein 1, sfrp3, Renal carcinoma antigen NY-REN-19, Metastasis, AA408040, Frezzled, Goal, STK11, Ovarian Epithelial Cancer, frzb-1, fiz, Neoplasm Metastases, fre, frp-3, neoplasm metastasis, Ovarian Epithelial Carcinomas, DmelCG9374, cancer metastasis, Ovarian Epithelial Cancers, FZRB, ovarian cancer, frzb-pen, Publication, sFRP-3, Ovarian, SFRP3, fzrb, Kinase, LKB1/PEUTZ JEGHERS KINASE, DmLKB1, anon-EST:Posey135, Phosphotransferase, FRZB-PEN, Epithelial, FRITZ, tumor cell migration, Frzb-1, Metastases., Fritz, par-4, Ovarian Cancer, Epithelial Cancer, Epithelial Carcinoma, metastasis, Transphosphorylase, Epithelial Ovarian Cancer, SRFP3, frtz, srfp3, Epithelial Ovarian, Ovarian Epithelial, FrzB-1, frzb1, PAR-4, Epithelial Ovarian Carcinoma, FRTZ, ATP Phosphotransferases, tumor metastasis, Par-4, ATP, Cancer, dlkb1, Carcinoma, Papers, hLKB1, CG9374, Metastases, Ovarian Epithelial Carcinoma, PJS, Liver kinase B1, Phosphotransferases, Metastase, Sfrp3, 2.7.11.1, Liver kinase B1 homolog, xfrzb, FRP-3, R75140, Neoplasm, fritz, Epithelial Ovarian Carcinomas, BBS15, FRZB-1, Epithelial Ovarian Cancers, FRZB1, hFIZ, Transphosphorylases, Lkb1, OS1, os1, Kinases, LKB1, ovarian epithelial cancer, Ovarian Carcinoma, C2orf86, frezzled, Manuscripts, xeek1, dLKB1, PAR4, FRE, mLKB1, c2orf86"],"pubmed_title_synonyms":["Regulations, tumor cell migration, FN, LETS Proteins, alpha 2 Surface Binding Glycoprotein, Formal Social Control, Proteins, Cold-Insoluble Globulins, Control, AW494241, neoplasm metastasis, alpha 2-Surface Binding Glycoprotein, Controls, Opsonic Glycoprotein, LETS, Social Controls, Omphk1, cancer metastasis, Concept, Social, Opsonic alpha(2)SB Glycoprotein, ARK5, Role Concept, Glycoprotein, Roles, Social Control, Cold Insoluble Globulins, AU014801, B230104P22Rik, Role Concepts, Fibronectin., Role, Concepts, regulation, Globulins, Cold-Insoluble, Opsonic, Regulation, tumor metastasis, Formal Social Controls"],"pubmed_abstract_synonyms":["Forms, Materials, Activity, determination, Metastasis, AA408040, Ass-1, Heterograft, Ovarian Epithelial Cancer, Gene Expression Profile, Cavity, Neoplasm Metastases, Profiles, neoplasm metastasis, TRANSPL HETEROL, Greater Sac, Ovarian Epithelial Carcinomas, phosphorylation, cancer metastasis, ter, Omental Bursa, dmTAF[[II]]230, greater peritoneal cavity, Background, ovarian cancer, suspension induced apoptosis, Glycoprotein, primary tumour, AA408052, Cultural, fold, 1, Analysis, DmLKB1, anon-EST:Posey135, multicellular organismal biosynthetic process, Mass Spectrum Analysis, Nesp2, ethnicity, single-organism biosynthetic process, Gene Expressions, TFIID TAF250, reference sample, Analyses, cel, FACT, anabolism, Iprit, par-4, Cold-Insoluble Globulins, hypoplasia, alpha 2-Surface Binding Glycoprotein, Signatures, ASS, Epithelial Ovarian, Ovarian Epithelial, CG14648, Xenotransplantations, Expression Signature, Cold Insoluble Globulins, Bsg75C, mustard gas, NUANCE, Transcriptomes, xenotransplant, Epithelial Ovarian Carcinoma, necrosis, Opsonic, Carcinoma, dTAF[[II]]230, Growl, Fibronectin, Ovarian Epithelial Carcinoma, Expression Profiles, TAF200, FNZ, TAFII-250, TAF250/230, Opsonic Glycoprotein, Spectrum Analysis, CIG, Spectroscopy, Gene Expression, Cultural Background, TAFII250, Liver kinase B1 homolog, bis(2-chloroethyl)sulfane, Cultures, Term, TRANSLOCATED PROMOTER REGION, Expression Signatures, Fn-1, R75140, Genetic Materials, ED-B, Expression Profile, Nesprin-2, Heterologous Transplantations, Genetic Material, Transcriptome Profiles, Xenograft, Xenotransplantation, FN, LETS Proteins, Cultural Beliefs, alpha 2 Surface Binding Glycoprotein, death rate, Transplantation, Spectrometry, INSDC_feature:gene, Xenografts, CG17603, TAF[[II]], Phenotypes, metastatic, Fn, Taf250, primary tumor, cavitas peritonealis, Material, SR3-5, nuclear pore anchor, Fibronectin., Cistron, xeek1, GFND, Globulins, TAF230, d230, Renal carcinoma antigen NY-REN-19, Transcriptome Profile, STK11, Gene, dTAFII250, biosynthesis, Spectrum Analyses, Yperite, Transplantations, EfW1, DmelCG9374, Omphk1, heterologous transplantation, Ovarian Epithelial Cancers, Opsonic alpha(2)SB Glycoprotein, ARK5, reduced, Ovarian, dmTAF1, Taf230, Mass, Bursa, Mustard gas, tiny, 1'-thiobis(2-chloroethane), LKB1/PEUTZ JEGHERS KINASE, Mass Spectroscopy, Backgrounds, Epithelial, TAF250, FACT80, tumor cell migration, OVCAR-8, Taf200, dTAF[[II]]250, Genetic, EOC cell, formation, cell, Profile, Ovarian Cancer, anon-WO0118547.126, Epithelial Cancer, Lesser, inhibiteur, Heterografts, AW494241, Epithelial Carcinoma, metastasis, Cultural Relativisms, Taf1p, Epithelial Ovarian Cancer, growl, NUA, Expressions, YUP8H12R_12, synthesis, bis(2-chloroethyl) sulphide, Lost, MSF, dTAF250, DmelCG4216, inhibidor, AU014801, time of survival, OVCAR.8, PAR-4, accidental cell death, YUP8H12R.12, Customs, DmelCG14648, Expression, culture, TAF, tumor metastasis, detachment induced cell death, Par-4, Heterologous, sulfur mustard, Controlled, Cancer, small, dlkb1, inhibitors, Controlling, TAF[[II]]250, Transcriptome, 1-chloro-2-[(2-chloroethyl)thio]ethane, hLKB1, CG9374, Metastases, TROPH, Proteins, Phosphorylations, EDMD5, inhibitor, l(3)84Ab, function, BG:DS00004.13, PJS, FINC, Cultural Backgrounds, Liver kinase B1, LETS, Cistrons, Cell, nev, E330027I09, dTAF230, whole transcriptome, Metastase, 2.7.11.1, MS, XENOTRANSPL, survival, Lesser Sac, p230, SYNE-2, Gene Expression Signatures, chemical analysis, Neoplasm, TAF[[II]]250/230, TFIID, Epithelial Ovarian Carcinomas, Sac, Gene Expression Signature, Cold-Insoluble, Death, Epithelial Ovarian Cancers, Mass Spectrum Analyses, Peritoneal, Taf[[II]]250, Mass Spectrum, TAF[[II]]230, ovarian epithelial cancer cell, Lkb1, underdeveloped, primary neoplasia, LKB1, CG4216, ovarian epithelial cancer, Senfgas, HETEROL TRANSPL, Ovarian Carcinoma, TAF[II]250, Omental, saccus serosus peritonei, DmelCG17603, AtTPR, Gene Expression Profiles, B230104P22Rik, T160, Relativisms, GFND2, assay, dLKB1, PAR4, Signature, mLKB1, Relativism, Cultural Relativism, Greater, General activity, TAF1"],"citation_count":["0"],"additional_accession":["PXD019223"]},"is_claimable":false,"name":"Fritz_STK11KO_MIB_2020_TripleTOF5600_complete","description":"The files are associated with a manuscript submitted for publication by Jamie Lee Fritz et al. The main goal of this paper was to identify potential substrates for LKB1, a master kinase that is required for epithelial ovarian cancer spheroid viability and metastasis. ","dates":{"publication":"Fri May 15 08:42:00 BST 2020"},"accession":"MSV000085415","cross_references":{"pubmed":["32429240"]}}