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FrejnoNot availableRectumColonic Cancer Cell LineColonRectal Cancer Cell LineKinobeads (KB) pulldowns (biological triplicates) were performed as described elsewhere (Medard et al., 2015), with minor modifications. Total Cell Lysates (TCLs) were quickly thawed at 37°C in a water bath and subsequently kept on ice. For each pulldown, 3 mL of 2.2 mg/mL TCL was transferred to pre-cooled ultracentrifuge tubes (Beckman & Coulter) and cleared by ultracentrifugation at 167,000 xg and 4°C for 20 min. Meanwhile, 35 µL of settled KBγ per TCL were distributed to separate wells of deep 96-well filter plates (Porvair Sciences), washed twice with 1 mL CP buffer (50 mM Tris/HCl pH 7.5, 5% Glycerol, 1.5 mM MgCl2, 150 mM NaCl, 1 mM Na3VO4) each and subsequently equilibrated using 1 mL CP buffer each, supplemented with 0.4% Igepal CA-630. Solvents were drained from the beads via gravitational flow through the filter unless stated otherwise. Afterwards, the plates were placed on regular 96-well plates for waste collection, centrifuged for 2 min at 240 xg and 4°C and sealed with the corresponding bottom sealing mat. Next, approximately 1.8 mL (equivalent of 4 mg of protein) of each TCL was transferred to its corresponding well, the plates were sealed with their top sealing mats and incubated for 60 min at 4°C on a head-over-end shaker. After lysate incubation, the plates were centrifuged for 3 min at 240 xg and 4°C, followed by drainage of the TCLs from the beads and three washing steps with CP buffer containing 0.4% Igepal CA-630 and two washing steps with CP buffer containing 0.2% Igepal CA-630. Subsequently the plates were centrifuged for 2 min at 240 xg on a 96-well plate for waste collection and sealed again with their bottom sealing mat. For elution of proteins bound to KBγ, 60 µL of 2x NuPAGE LDS sample buffer (Thermo Fisher) per well containing 50 mM DTT were distributed to the filter plates, the plates were sealed with their top sealing mats and incubated for 30 min at 50°C and 700 rpm in a thermomixer. Afterwards, the top and bottom sealing mats were removed, the filter plates were placed onto 96-well plates for eluate collection and centrifuged for 2 min at 670 xg and 4°C. Free sulfhydryl groups were then alkylated for 30 min at room temperature protected from light by addition of chloroacetamide to a final concentration of 55 mM. Finally, detergents and salts were removed from eluates by running a short electrophoresis (approximately 0.5 cm) using 4−12% NuPAGE gels (Thermo Fisher), followed by tryptic in-gel digestion according to standard procedures.PrideBernhard KusterLTQ Orbitrap VelosPARTIALChair of Proteomics and Bioanalytics, Technische Universität München, Germany29101300 Frejno M, Zenezini Chiozzi R, Wilhelm M, Koch H, Zheng R, Klaeger S, Ruprecht B, Meng C, Kramer K, Jarzab A, Heinzlmeir S, Johnstone E, Domingo E, Kerr D, Jesinghaus M, Slotta-Huspenina J, Weichert W, Knapp S, Feller SM, Kuster B. Pharmacoproteomic characterisation of human colon and rectal cancer. Mol Syst Biol. 2017 13(11):951 10.15252/msb.20177701TUMkuster@tum.deMass SpectrometryShotgun proteomicsRectum CancerColon CancerPatient stratificationCorrelation of mrna and protein abundanceCrc65Quasar2Personalised medicineIntegrated full proteome subtypesMass spectrometryConsensus molecular subtypesCptacKinobeadshttp://www.ebi.ac.uk/pride/archive/projects/PXD005355MS1 intensity based label-free quantification methodiodoacetamide derivatized residuemonohydroxylated residueacetylated residueMaxQuant v.1.5.3.30 was used to search our Kinobeads raw data against UniProtKB (v25.11.2015; 92,011 sequences), concatenated with a list of common contaminants supplied by MaxQuant (245 sequences) in two separate runs with identical settings. We set the digestion mode to fully tryptic, allowing for cleavage before proline (Trypsin/P) and a maximum of two missed cleavages. Carbamidomethylation of cysteines was set as a fixed modification and oxidation of methionines, as well as acetylation of protein N-termini were set as variable modifications, allowing for a maximum number of 5 modifications per peptide. Candidate peptides were required to have a length of at least 7 amino acids, with a maximum peptide mass of 4,600 Da. The fragment ion tolerance was set to 120 ppm for FTMS. A first search with a precursor ion tolerance of 20 ppm was used to recalibrate raw data based on all peptide-spectrum-matches (PSMs) without filtering using hard score cut-offs. After recalibration, the data were searched with a precursor ion tolerance of 4.5 ppm, while chimeric spectra were searched a second time using MaxQuant’s “Second peptides” option to identify co-fragmented peptide precursors. We used “Match between runs” with an alignment time window of 30 min and a match time window of 1.1 min to transfer identifications between raw files of the same and neighbouring fractions (± 1 fraction). Using the classical target-decoy approach with a concatenated database of reversed peptide sequences, data were filtered using a PSM and protein false discovery rate (FDR) of 1%. Protein groups were required to have at least one unique or razor peptide, with each razor peptide being used only once during the calculation of the protein FDR. No score cut-offs were applied in addition to the target-decoy FDR. We used unique and razor peptides for quantification, discarding the unmodified counterparts of peptides harbouring oxidated methionines and acetylated protein N-termini.ProteomicsHomo Sapiens (human)martin.frejno@tum.deBiomedicalGermanyMost molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome-guided pre-clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,074 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to, for example, facilitate the design of innovative prospective clinical trials.Pharmacoproteomic characterisation of human colon and rectal cancer.Frejno Martin M, Zenezini Chiozzi Riccardo R, Wilhelm Mathias M, Koch Heiner H, Zheng Runsheng R, Klaeger Susan S, Ruprecht Benjamin B, Meng Chen C, Kramer Karl K, Jarzab Anna A, Heinzlmeir Stephanie S, Johnstone Elaine E, Domingo Enric E, Kerr David D, Jesinghaus Moritz M, Slotta-Huspenina Julia J, Weichert Wilko W, Knapp Stefan S, Feller Stephan M SM, Kuster Bernhard BCPD photolyase activity, IL1BC, PhrB photolyase activity, Laundry Pods, Synthetic Detergents, CASP-1, classic hairy cell leukaemia, CG7788, crice, Syndet, CSMF, Visible Light, Hydrogenchlorid, NP-40, protein, apg, pigmented epithelium, mg/ml, FabD, Solvent, dmTAF[[II]]230, Detergent, protein polypeptide chains, Pod, Synthetic Detergent, halite, hydrogen chloride, Glycerol, Magnesium chloride, Detergents, P-mad, hnu, ionic compounds, HCL-C, 1, 2, 3, Min, NUP96, outer pigmented layer of retina, protein aggregate, Il1bc, epithelium, Smad, foton, DmelCG42273, 3-Propanetriol, Oelsuess, malonyl-CoA:ACP transacylase activity, TFIID TAF250, cel, P-Mad, Salt, pigmented retina, SAMS, min, mAPC, proteins, Heads, Salz, sel, free, IL-1BC, DNA cyclobutane dipyrimidine photolyase activity, T2, SUPPRESSOR OF AUXIN RESISTANCE 3, salts, AI047805, cloruro sodico, dMAD, dMad, salt, NOR-1, pigment epithelium of retina, Wasserstoffchlorid, Non-Idet P-40, ICE, p-Mad, sample, pigmented retina epithelium, head (volume), gamma, malonyl transferase activity, Glyceritol, PRE, Detergent Pod, dTAF[[II]]230, rock salt, TX-144 surfactant, Radiation, CHN, Caspase-1 subunit p10, malonyl-CoA:AcpM transacylase activity, ice, iCE, drice, eluted material, SAMS1, [MgCl2], deoxyribonucleic cyclobutane dipyrimidine photolyase activity, ORF 3617, detergent, TAF200, Dmel_CG7826, Light, TAFII-250, pigmented retinal epithelium, classic hairy cell leukemia, TAF250/230, DmelCG7788, shortened, MgCl2, TAFII250, common salt, LIGHT, retinal pigment, Dm1, drIce, drICE, glycerol, HCL, Chlorwasserstoff, THIL, dipyrimidine photolyase (photosensitive), Laundry Detergent Pod, Cleansing Agents, leukemic reticuloendotheliosis, END, Detergent Pods, retinal pigment layer, Dmel_CG7835, Triton X-114, Mnb, MNB, Visible Radiations, deep, Gro, PMad, Visible Radiation, HVEML, Pods, glycerine, ionic compound, retinal pigmented epithelium, P45, HCl, En(vvl), AW124434, AI046368, CG17603, natrii chloridum, lysed material, TAF[[II]], pSmad, CG12399, magnesium dichloride, chloracetamide, phr A photolyase activity, light quantum, DNA-photoreactivating enzyme, Agents, Taf250, SR3-5, Drice, p45, pMAD, pMad, chlorane, DRICE, short, acyl-carrier-protein S-malonyltransferase activity, TAF230, GLYCEROL, d230, MATA1, Laundry Detergent Pods, chlorure d'hydrogene, DrIce, DrICE, malonyl coenzyme A-acyl carrier protein transacylase activity, Gene, dTAFII250, [acyl-carrier protein] S-malonyltransferase activity, photoreactivating enzyme activity, ACP S-malonyltransferase activity, protein-containing complex, EfW1, deoxyribodipyrimidine photolyase activity, CG7826, stratum pigmentosum retinae, Buffer, Ly113, Agent, Glycerine, glycyl alcohol, potassium salt, Propanetriol, 2/23, polypeptide chain, dmTAF1, Taf230, malonyl transacylase activity, Trihydroxypropane, AdoMet, CG7835, Gene Products, CG42273, MAD, stratum pigmentosa retinae, light, cloruro de hidrogeno, TAF250, MAT, Mat, Synthetic, Taf200, MOS3, dTAF[[II]]250, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, AI573420, PRECOCIOUS, propane-1, Hydrogen chloride, cell, Lichtquant, scattered, cephalic area, Glycerin, malonyl-CoA:acyl-carrier-protein S-malonyltransferase activity, PCE-2, mad, F23A5.3, chlorure de sodium, stubby, Taf1p, Sciences, Visible, Laundry Detergent, E(zen)2, dTAF250, l(2)k00237, lysate, hairy cell leukemia, glycerolum, Caspase-1 subunit p20, sels, Kochsalz, Smad1, photon, Laundry Pod, TR2, TAF, F23A5_3, HHT1, Laundry, NOR1, DYRK1, Nor1, TAF[[II]]250, Magnesiumchlorid, caspase 3, diffuse, protein complex, Glyzerin, acyl carrier protein malonyltransferase activity, sales, malonyl-CoA:acyl carrier protein transacylase activity, Proteins, 3-triol, l(3)84Ab, Igepal CA-630, BG:DS00004.13, chloridohydrogen, CE-2, buffer, CD258, Cell, dTAF230, [HCl], Electrophoreses., stratum pigmentosum (retina), MODIFIER OF SNC1, Ams, native protein, Temperatures, Natriumchlorid, acyl carrier proteinmalonyltransferase activity, natural protein, p230, Protein, deoxyribonucleic photolyase activity, Hydrochloride, TAF[[II]]250/230, TFIID, table salt, Dyrk1, CES2A1, NaCl, Magnesium chloride anhydrous, Cleansing, Radiations, Taf[[II]]250, AU020952, 3-Trihydroxypropane, RPE, TAF[[II]]230, waterbath, MINOR, photolyase activity, ACAT, HVEM-L, CC1, Photoradiation, TAF[II]250, IL-1 beta-converting enzyme, Salze, Interleukin-1 beta-converting enzyme, retinal pigment epithelium, sample population, LTg, p. pigmentosa retinae, ME-IV, sal, Interleukin-1 beta convertase, Protein Gene Products, Gene Proteins, l(2)K00237, DmelCG17603, Photoradiations, DmelCG12399, c28, Cleansing Agent, malonyl-CoA-acyl carrier protein transacylase activity, concentration, Nonidet P-40, MCAT activity, 3.4.22.36, TEC, deoxyribonucleate pyrimidine dimer lyase (photosensitive), ORW1, adult head, Runnings, Minor, hydrochloric acid, TAF1, sodium chloridemalignant neoplasm of the rectum, malignant rectal neoplasm, Rectal Neoplasm, Rectal, malignant tumor of rectum, human being, carcinoma of the rectum, Rectum Neoplasm, rectum carcinoma, Rectal Cancers, Neoplasms, malignant rectum tumor, malignant rectum neoplasm, Tumor, Appendix Epiploica, hindgut, Rectum Cancers, rectal carcinoma, malignant tumour of the rectum, large bowel, Rectum Neoplasms, rectum cancer, Taenia Coli, Appendix, Neoplasm, Rectum Cancer, Rectum, Omental Appendices, Omental Appendix, Cancer of the Rectum, malignant rectal tumour, posterior intestine, Appendices, malignant tumour of rectum, Omental, cancer of rectum, man, human, malignant neoplasm of rectum, Rectal Tumors, Rectal cancer, rectal cancer, Cancer of Rectum., COLON, carcinoma of rectum, Rectal Cancer, malignant tumor of the rectum, Rectal Tumor, cancer of the rectum, malignant rectum tumour, malignant rectal tumor, CancerSH2-Bb, Bru, IPP2A2, Raw, Aminosaeure, firm, cleavage, Irip, Amino acid, protein, NAALAdase, Long Term, 5730420M11Rik, peptide, Polypeptides, Cut, NAALADase I, protein polypeptide chains, FOLH, Drug Tolerance, ClvPrd, peptido, l(1)7Ba, l(1)7Bb, L-Proline, C530001K22Rik, impenetrable, Min, 3.4.17.21, protein aggregate, Effect, WMS, DmelCG42273, Svc, SH2-B, somitogenic mesoderm, SET, F, amino acids, peptides, Membrane glutamate carboxypeptidase, TAF-I, phosphatase 2A inhibitor I2PP2A, min, mAPC, proteins, number of, NAALAD1, CG11387, Folylpoly-gamma-glutamate carboxypeptidase, DmelCG4299, AI047805, set, IGAAD, DmelCG10574, ppm, CT, s, GPHYSD2, Long-Term Effects, drug tolerance, SGS, ratio, phapii, unsegmented mesenchyme, immune system tolerance, Aminokarbonsaeure, T5E21.12, acetylation, Ct, Longterm Effect, Dmel_CG7826, StF-IT-1, extra or missing physical or functional parts, SH2-B PH domain-containing signaling mediator 1, fragmented, alpha-amino carboxylic acids, ACMICD, Dm1, PSM, Psm, Immunologic Tolerance, BcDNA:GH10590, presumptive somite mesoderm, Prostate-specific membrane antigen, Dmel_CG7835, T5E21_12, parent ion, Mnb, MNB, Amino Acid, Acid, Pteroylpoly-gamma-glutamate carboxypeptidase, HLA-DR-associated protein II, Amino acids, DI-2, I-2Dm, FGCP, cracked, proportionality, common, rate, CG4299, MASS, inhibitor of granzyme A-activated DNase, AW124434, I-2PP1, Pro-rich, TAF-IBETA, Self Tolerance, Tolerance, precursor ion, PSMA, TAF-Ibeta, Acids, Polypeptide, i2pp2a, time, SH2 domain-containing protein 1B, l(1)VE614, Effects, False, fractured, number, Aminocarbonsaeure, unsegmented paraxial mesoderm, FBN, alpha-amino acid, precursor, protein-containing complex, somitomeric mesoderm, GCPII, PHAPII, CG7826, period, template-activating factor I, polypeptide chain, ECTOL1, tough, CG7835, CG42273, N-acetylated-alpha-linked acidic dipeptidase I, mKIAA1299, Del(8)44H, SH2B, proportion, Longterm, ipp2a2, Acetylations, 2pp2a, mGCP, Long-Term, kf, CG10574, OCTD, 2PP2A, 10^[-6], DmelCG11387, taf-ibeta, L Proline, has or lacks parts of type, dSET, dSet, peptidos, Long-Term Effect, data, DYRK1, protein complex, igaad, split, alpha-amino acids, backward, Peptide, GCP2, mereological quality, Glutamate carboxypeptidase II, polypeptide, Cell growth-inhibiting gene 27 protein, native protein, Immune Tolerance, natural protein, I-2PP2A, Dm I-2, Protein, Long Term Effects, I2PP2A, hemorrhaged, MFS1, Dyrk1, segmental plate, Sh2bpsm1, WMS2, Data Base, torn, AU020952, PH and SH2 domain-containing signaling mediator, Col4a-1, Protein., CC1, Amino, Longterm Effects, Folate hydrolase 1, ME-IV, incised, dSET/TAF-Ibeta, 2610030F17Rik, cardinality, SSKS, AI425885, quotient, Peptid, variable, AA407739, reversed, Immunological TolerancePRKMK1, malignant Growth, carcinoma of large bowel, malignant tumour of large bowel, 2410041A17Rik, ACTG, ACTE, neoplasia, Eyk, fs(1)M34, protein, MITOGEN ACTIVATED PROTEIN KINASE KINASE 1, colorectal carcinoma cell, Tumor, F20O9_210, Technic, Act5, csp2, l(1)G0420, DmelCG12051, protein polypeptide chains, Techniques, Immunogold-Silver Techniques, Associations, malignant large intestine tumor, Immunogold-Silver Technique, F20B18.180, Line, HEL-176, CG4601, Analysis, protein aggregate, malignant neoplasm of the large intestine, Atf4, ATMEK1, 929, Mass Spectrum Analysis, A, DmelCG8669, C, cyt5C, DHO, Analyses, cell process disease, tumor disease, neoplasm (disease), malignant colorectal tumor, F20O9.210, CG18572, MAP kinase kinase 4 activity, proteins, CRUCIFERIN C, CA, large intestine cancer, MEKK1, Immunogold-Silver Technic, malignant neoplasm, medicine, act 42A, data., MKK, MAPK activator activity, Ac5C, Immunolabeling Technique, CG4027, ACT, Act, tumor, Immunogold Technics, somatic mutation, colorectal (colon or rectal) cancer, Tumors, malignancy, l(1)G0330, Actin/BAP47, CTE-II, AACT, potp, CTE-IIa, Immunogold Technique, act, carcinoma of the large intestine, Ach1, hBACH, ACH1, neoplastic disease, large intestine carcinoma, LACH1, somatic, malignant large intestine neoplasm, Spectrum Analysis, tumours, act42A, Spectroscopy, GIG25, Immunogold, Immunogold Techniques, malignant neoplasm of large intestine, Immunolabeling Technic, nmf12, Alpha-1-antichymotrypsin His-Pro-less, Su(b), AFFX-Dros-ACTIN_M_r_at, organ system cancer, Immunolabeling Technics, DFNA26, actin, Technics, l(2)crc, LACH, DFNA20, GAT, anon-EST:fe3D7, Lines, cruciferin 3, DmelCG4027, l(1)G0117, MAP2K, susceptibility to, MRE4, Spectrometry, MAP kinase kinase 7 activity, Actin, Immunogold Silver Techniques, ERK activator kinase activity, beta-actin/Bap47, cancer of large bowel, l(1)G0486, malignant neoplasm of the large bowel, ATF-4, tumour disease, l(1)G0245, actin5C, l(1)G0009, Patient, malignant colorectal tumour, MITOGEN ACTIVATED PROTEIN KINASE KINASE, ACTL3, Lach1, colorectal carcinoma, malignant neoplasm of colorectum, malignant tumour of the large bowel, malignant tumour of large intestine, cancer of the large bowel, CG8669, cancer of large intestine, mKIAA0147, ATF4/crc, other neoplasm, cancer, BACH, MEK1, Mek1, Proteomes, MEK2, AI118201, l(1)Ab, Act5c, Immunogold-Silver, advanced, l(1)G0010, Clr, MAPKK1, cell type cancer, Neoplasms, MAP kinase/ ERK kinase 1, ACT5C, CG12051, carcinoma of colorectum, Gene, Serpin A3, malignant large bowel neoplasm, Spectrum Analyses, protein-containing complex, Bach, autosomal dominant, NEOPL, l(1)G0025, colorectal cancer, polypeptide chain, dATF-4, colorectum cancer, resistance, Gene Products, Mass, Cell growth-inhibiting gene 24|25 protein, anon-EST:Liang-2.17, anon-EST:Liang-2.11, clone 2.11, neoplasm, Technique, malignant tumour, Mass Spectroscopy, Immunogold Silver Technics, MKK1, MKK2, MKK4, act5C, malignant large intestine tumour, clone 2.17, large bowel carcinoma, MKK6, BRWS2, MKK7, malignant tumour of the large intestine, Scrb1, CG9429, tumour, Ire1, fs(1)829, cancer of the large intestine, anon-EST:fe2D2, Act42a, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), drugs, 1700027G07Rik, malignant colorectal neoplasm, time of survival, DmelCG18572, Clients, vartul, T11, carcinoma of the large bowel, carcinoma of large intestine, STK27, Act-5C, NMAPKK, Cte-II, Neoplastic Growth, l(1)G0177, malignant tumor of the large bowel, ATP:protein phosphotransferase (MAPKKK-activated) activity, mitogen-activated protein kinase kinase activity, 42A, malignant tumor of large intestine, data, CPS, malignant large bowel tumor, Immunogold Technic, protein complex, malignant, SCRIB1, Proteins, dJ393D12.2, Cell Lines, total expressed protein, Immunohistocytochemistry, malignant neoplasm of large bowel, function, eth, MAP kinase or ERK kinase activity, Client, Cell, neoplastic growth, MT, CAD, survival, native protein, natural protein, beta-actin, MEK activity, malignant neoplasm (disease), Protein, cancer of colorectum, M32055, Act42, CRC, Crc, ACTA3, Mer, Mass Spectrum Analyses, CRC cell, Immunolabeling, l(1)G0079, large bowel cancer, colorectal cancer with chromosomal instability, Mass Spectrum, primary cancer, Immunocytochemistry, malignant tumor of large bowel, MAPKK, PYR1, VSCM, MAPKK activity, colorectum carcinoma, act 5C, malignant colorectum neoplasm, crc, Prkmk1, CRIB, disease of cellular proliferation, malignant tumor, Protein Gene Products, Nyk, DmelCG9429, Gene Proteins, crt, colon cancer, malignant neoplastic disease, F20B18_180, CFC3, Immunogold-Silver Technics, Immunolabeling Techniques, DRORUD, malignant tumor of the large intestine, BAP47, ACTSG, Bap47, malignant large bowel tumour, NEOPLASMS BENIGN, Neoplasia, Actin5CPRKMK1, malignant Growth, carcinoma of large bowel, CPD photolyase activity, malignant tumour of large bowel, PhrB photolyase activity, 2410041A17Rik, ACTG, ACTE, neoplasia, Eyk, fs(1)M34, protein, MITOGEN ACTIVATED PROTEIN KINASE KINASE 1, colorectal carcinoma cell, Tumor, pigmented epithelium, F20O9_210, Technic, Act5, csp2, l(1)G0420, DmelCG12051, protein polypeptide chains, Techniques, Immunogold-Silver Techniques, Associations, malignant large intestine tumor, Immunogold-Silver Technique, F20B18.180, Line, HEL-176, CG4601, 3, NUP96, Analysis, outer pigmented layer of retina, protein aggregate, epithelium, malignant neoplasm of the large intestine, Atf4, ATMEK1, 929, Mass Spectrum Analysis, A, DmelCG8669, C, cyt5C, DHO, Analyses, cell process disease, tumor disease, neoplasm (disease), malignant colorectal tumor, pigmented retina, F20O9.210, CG18572, MAP kinase kinase 4 activity, proteins, CRUCIFERIN C, DNA cyclobutane dipyrimidine photolyase activity, CA, large intestine cancer, SUPPRESSOR OF AUXIN RESISTANCE 3, MEKK1, pigment epithelium of retina, Immunogold-Silver Technic, malignant neoplasm, medicine, act 42A, data., MKK, MAPK activator activity, Ac5C, Immunolabeling Technique, CG4027, pigmented retina epithelium, ACT, Act, tumor, Immunogold Technics, somatic mutation, colorectal (colon or rectal) cancer, Tumors, PRE, malignancy, l(1)G0330, Actin/BAP47, CTE-II, AACT, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, potp, CTE-IIa, Immunogold Technique, act, carcinoma of the large intestine, Ach1, hBACH, ACH1, neoplastic disease, large intestine carcinoma, pigmented retinal epithelium, LACH1, somatic, malignant large intestine neoplasm, Spectrum Analysis, tumours, act42A, Spectroscopy, GIG25, Immunogold, Immunogold Techniques, malignant neoplasm of large intestine, Immunolabeling Technic, retinal pigment, nmf12, Alpha-1-antichymotrypsin His-Pro-less, Su(b), AFFX-Dros-ACTIN_M_r_at, organ system cancer, Immunolabeling Technics, DFNA26, dipyrimidine photolyase (photosensitive), actin, Technics, l(2)crc, LACH, DFNA20, GAT, retinal pigment layer, anon-EST:fe3D7, Lines, cruciferin 3, DmelCG4027, retinal pigmented epithelium, l(1)G0117, MAP2K, susceptibility to, MRE4, Spectrometry, MAP kinase kinase 7 activity, Actin, Immunogold Silver Techniques, ERK activator kinase activity, beta-actin/Bap47, cancer of large bowel, l(1)G0486, malignant neoplasm of the large bowel, ATF-4, tumour disease, l(1)G0245, phr A photolyase activity, actin5C, DNA-photoreactivating enzyme, l(1)G0009, Patient, malignant colorectal tumour, MITOGEN ACTIVATED PROTEIN KINASE KINASE, ACTL3, Lach1, colorectal carcinoma, malignant neoplasm of colorectum, malignant tumour of the large bowel, malignant tumour of large intestine, cancer of the large bowel, CG8669, cancer of large intestine, mKIAA0147, ATF4/crc, other neoplasm, cancer, BACH, MEK1, Mek1, Proteomes, MEK2, AI118201, l(1)Ab, Act5c, Immunogold-Silver, advanced, l(1)G0010, Clr, MAPKK1, cell type cancer, Neoplasms, MAP kinase/ ERK kinase 1, ACT5C, CG12051, carcinoma of colorectum, Gene, Serpin A3, malignant large bowel neoplasm, Spectrum Analyses, photoreactivating enzyme activity, protein-containing complex, Bach, autosomal dominant, deoxyribodipyrimidine photolyase activity, stratum pigmentosum retinae, NEOPL, l(1)G0025, colorectal cancer, polypeptide chain, dATF-4, colorectum cancer, resistance, Gene Products, Mass, Cell growth-inhibiting gene 24|25 protein, anon-EST:Liang-2.17, stratum pigmentosa retinae, anon-EST:Liang-2.11, clone 2.11, neoplasm, Technique, malignant tumour, Mass Spectroscopy, Immunogold Silver Technics, MKK1, MKK2, MKK4, act5C, MOS3, malignant large intestine tumour, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, PRECOCIOUS, clone 2.17, large bowel carcinoma, MKK6, BRWS2, MKK7, malignant tumour of the large intestine, Scrb1, CG9429, F23A5.3, tumour, Ire1, fs(1)829, cancer of the large intestine, anon-EST:fe2D2, Act42a, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), drugs, 1700027G07Rik, malignant colorectal neoplasm, time of survival, DmelCG18572, Clients, vartul, T11, carcinoma of the large bowel, carcinoma of large intestine, STK27, Act-5C, NMAPKK, Cte-II, F23A5_3, Neoplastic Growth, l(1)G0177, malignant tumor of the large bowel, ATP:protein phosphotransferase (MAPKKK-activated) activity, mitogen-activated protein kinase kinase activity, 42A, malignant tumor of large intestine, data, CPS, malignant large bowel tumor, Immunogold Technic, protein complex, malignant, SCRIB1, Proteins, dJ393D12.2, Cell Lines, total expressed protein, Immunohistocytochemistry, malignant neoplasm of large bowel, function, eth, MAP kinase or ERK kinase activity, Client, Cell, stratum pigmentosum (retina), MODIFIER OF SNC1, neoplastic growth, MT, CAD, survival, native protein, natural protein, beta-actin, MEK activity, malignant neoplasm (disease), Protein, cancer of colorectum, M32055, deoxyribonucleic photolyase activity, Act42, CRC, Crc, ACTA3, Mer, Mass Spectrum Analyses, CRC cell, Immunolabeling, l(1)G0079, large bowel cancer, colorectal cancer with chromosomal instability, Mass Spectrum, primary cancer, Immunocytochemistry, RPE, malignant tumor of large bowel, MAPKK, photolyase activity, PYR1, VSCM, MAPKK activity, colorectum carcinoma, act 5C, malignant colorectum neoplasm, crc, Prkmk1, CRIB, retinal pigment epithelium, disease of cellular proliferation, malignant tumor, p. pigmentosa retinae, Protein Gene Products, Nyk, DmelCG9429, Gene Proteins, crt, colon cancer, malignant neoplastic disease, F20B18_180, CFC3, Immunogold-Silver Technics, Immunolabeling Techniques, DRORUD, malignant tumor of the large intestine, BAP47, deoxyribonucleate pyrimidine dimer lyase (photosensitive), ACTSG, Bap47, malignant large bowel tumour, NEOPLASMS BENIGN, Neoplasia, Actin5Cmalignant neoplasm of the rectum, malignant rectal neoplasm, Rectal Neoplasm, Rectal, malignant tumor of rectum, human being, carcinoma of the rectum, Rectum Neoplasm, rectum carcinoma, Rectal Cancers, Neoplasms, malignant rectum tumor, malignant rectum neoplasm, Tumor, Appendix Epiploica, hindgut, Rectum Cancers, rectal carcinoma, malignant tumour of the rectum, large bowel, Rectum Neoplasms, rectum cancer, Taenia Coli, Appendix, Neoplasm, Rectum Cancer, Rectum, Omental Appendices, Omental Appendix, Cancer of the Rectum, malignant rectal tumour, posterior intestine, Appendices, malignant tumour of rectum, Omental, cancer of rectum, man, human, malignant neoplasm of rectum, Rectal Tumors, Rectal cancer, rectal cancer, Cancer of Rectum., COLON, carcinoma of rectum, Rectal Cancer, malignant tumor of the rectum, Rectal Tumor, cancer of the rectum, malignant rectum tumour, malignant rectal tumor, Cancer323truePharmacoproteomic characterisation of human colon and rectal cancer - CRC65 KinobeadsMost molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of >10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients, as well as transcriptomes of 145 cell lines and 89 patients defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,000 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data to the community to e.g. facilitate the design of innovative prospective clinical trials.2017-12-122017-12-12PXD005355280655164609918049851114542249215684354407128421832704236333635119834300663636275838569636368888111430155571145263145262364934613126957366649239161936411066568895113636476272366111232944222955583232312258636543460792519365914320597129386558191250232119577481866196821586722568076175543735925366840816918045427877512010892250583674147956410039236942049433445974142001293529367156759364386771605404831315282693045627163916242920427794476237612181003296293948840479NCBITaxon:21571315273105106720596872016516173630969893610478214836432042106132049138169374327732046453511110321745921612928867128867641006945694101676341021076127735113165821358430141729817463367541287356756840301350621813019411192943936711041136445932025301270104759412047886134749515372110971652998279051398031758543980126086639808137575551832019644711141554219325552113834399813981810269701069955529NCBITaxon:47518502983354764146547798251021699823897648407413735186287054824153NCBITaxon:50557984467525100036433414754803597413708115466547898353221599838106771034819852348780422531488414222863479461571871599191572952929211752719860148840633424951869123423515233598589859886559746499870392021110723635272159874190828743418235024145113969293190259390719017463601237474636172262536001319722119158531058859698951105198997237989772000263419610264266722758858156899628737562690724420237172019998570724074767927459615333554319313355418400513686150596866628666134751536329NCBITaxon:17632862873488376705802718481865368595105135294296110098402321000734882412336363071047005187878945556449447NCBITaxon:13356265419591399878168119011478281055524NCBITaxon:96061358584690081979153519307285930085290051184995262254121337591390143811139442370412044143708351581990119519532590841370137023943222774862615835583715371633376057267998086371137121906503714759172073127262981274575727090309031372814243371421044792491108239412NCBITaxon:961514780269266100658137352750454135663816475203750644223669502129349790546322455525365199764990814389923745374726473237602647312887055955362527403271602938511497864794362938247943722511775299167387193844137659393432715910022637674234442345467001287689591198467041464792936528034280382803510803481793922950271131681911265269971028621076015973611431140981087135547743658142450722953379698204232124223321803369822347081645733165467599287770203829314125295508114817448886437452649997283035718308550717629970767892683704151562887651388563924561152086595551655181135491432137159749535026143213858781194963401614280053164610466038151845474485009747711805124017484185560155547920427420148871105325329726100594128909316435990013894382835423242331220585604162991311227317018799152678181871049316407299467303337330485264638301130641399253064236121162065261610337286129940207340115357652611114716133865431201725323712552329935316317NCBITaxon:11084993841063267872862321933486208621160791392227681196125522814953932132232334774121827532917573129948861814084341033519963139248811533811533933043937556992862633911209488624157183997586444237486435332444260665332413439097682127178637863999839986865535291486541042986357358257632884019864982380102868899958665220341632138119380625631886571303443112130886581144889198466645463NCBITaxon:11072NCBITaxon:11071142800628835374375116597145943116598854331116781077854314408043933434NCBITaxon:1108269397738218993182443193512838714595311688538695berry8694869724436647015011142869215047514991054842047147251208470146497444974311700893062186441930611076323308056603960162179748258539460553965132127905688133775129817660171121478610502366946532051124501897441739412450128853183889198679488531911137910371647351660152943631631198573896939343237956026087121346334323223544314275241433611334565560291699636436802790105603140818838185733703401881274414437552162038713985584081724055986091838272759212744234081702759812744201274426235455382117627594328247480119915095648188229120455148167238473848190695148498101510693731263753405203860186497405224052141856451804NCBITaxon:813478009152275484793870333849917226175610946161435120325812055052352594473205493864651213880376686120678112202230741867051186705738733486912193879186802398007186801215451468351408186150847120677769183885160861138886915216778672127901008704351231719692812392948677133226126219813188268241122926571632957693812471246148545132838834839294911390363120416266589077151488003694169436945187901015080817053942065421055687317447127015329242814111946691169601454586953201019812646905505371408157697392830312383911283128212802811010832825253531522811235315349825741948153623142410145481NCBInr 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