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Adelaiye-Ogala"],"technology_type":["Mass Spectrometry","Top-down proteomics"],"disease":["Prostate Adenocarcinoma"],"software":[""],"submitter_keywords":["Mecom","Evi1-mds1 complex","Androgen receptor","Epigenetics","Castration-resistance","Prostate cancers","Enzalutamide-resistance","Non-canonical ar","Drug resistance","Parpi"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD062331"],"tissue":["Epithelial Cell","Cell Culture"],"sample_protocol":["Samples were collected and treated with lysis buffer [50 mM Tris-formic acid (FA), 150 mM NaCl, 0.5% sodium deoxycholate, 2% SDS, 2% IGEPAL CA-630 (pH 8.4)], supplemented with cOmplete protease inhibitor tablets. The mixture was homogenized using a 5-second burst on a Polytron homogenizer (Kinematica AG, Switzerland), followed by 5 seconds on ice. This process was repeated twice. The samples were then sonicated with a high-energy sonicator set to 'high' (level 14 on the Qsonica XL-2000 model), using a 5-second burst followed by 5 seconds on ice. This sonication step was repeated three times. After sonication, samples were allowed to settle on ice for 30 minutes before being centrifuged at 20,000g for 30 minutes at 4°C. The supernatant was carefully collected, and the protein concentration of each sample was determined using the bicinchoninic acid (BCA) assay (Thermo Fisher Scientific, Waltham, MA). Proteins were reduced with 10 mM dithiothreitol at 56°C for 30 minutes and alkylated with 20 mM iodoacetamide at 37°C for 30 minutes in the dark. Both reduction and alkylation steps were carried out with constant vortexing in a Thermomixer at 550 rpm. Protein precipitation was performed by adding 1 and 5 volumes of chilled acetone followed by vortexing, and the mixture was incubated at -20°C for 3 hours. After centrifugation at 20,000 g for 30 minutes at 4°C, the supernatant was discarded, and the protein pellets were washed with 200 µL methanol. The protein pellets were reconstituted in 50 mM Tris-FA. Trypsin (Sigma-Aldrich), activated with 50 mM Tris-FA, was added to the protein pellets at a protein to trypsin ratio of 20:1, and tryptic digestion was carried out at 37°C overnight with constant vortexing. Digestion was terminated by adding 1% FA. The samples were then centrifuged at 20,000 g for 30 minutes at 4°C, and the supernatants were carefully transferred to LC vials. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted using a trapping nano-flow LC-Orbitrap Astral MS system, which comprised a Dionex Ultimate 3000 nano LC system, a Dionex Ultimate 3000 gradient micro-LC system with a WPS-3000 autosampler, and an Orbitrap Astral mass spectrometer (Thermo Fisher Scientific, Waltham, MA). A single injection of 500 ng derived peptides was analyzed for each sample. A trapping column (100 µm ID × 5 cm, packed with 5µm C18, CoAnn Technologies, Richland, WA) was employed prior to nano LC column (75 μm ID × 30 cm, packed with 1.7 μm C18, CoAnn Technologies, Richland, WA) separation for matrix component removal and selective peptide delivery. Mobile phases A and B were 0.1% formic acid (FA) in 2% acetonitrile, and 0.1% FA in 88% acetonitrile, respectively. The LC gradient profile was as follows: 4-35% B for 39 min; 35% to 97% B for 0.1 min; and isocratic at 97% B for 3 min. Mass spectrometry operated in data-independent acquisition (DIA) mode. MS1 spectra were acquired in the m/z range of 380 to 980 at a resolution of 180k. The normalized Automatic Gain Control (AGC) target for MS1 was set at 500%, with a maximum injection time of 5 ms. Precursor ions were isolated using a 4-Th wide window and fragmented by higher-energy collision-induced dissociation (HCD) at a normalized collision energy of 25%. MS2 spectra were acquired in the Astral (AST) mass analyzer. The normalized Automatic Gain Control (AGC) target was set at 200%, with a maximum injection time of 8 ms."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["For protein identification and quantification, the MS raw files were analyzed by searching against the Uniprot-SwissProt Human database (accessed April 2023, containing 20,422 protein entries) using DIA-NN (v1.8.1) in library-free mode. Trypsin was selected as the protease with one allowed missed cleavage. Cysteine carbamidomethylation was set as a static modification, while variable modifications included methionine oxidation and N-terminal acetylation. The precursor and protein FDR% was set to 1%. Mass accuracy was set to 4 ppm for MS1 and 5 ppm for MS2. The scan window was set to 9."],"omics_type":["Proteomics"],"labhead":["Remi adelaiye-Ogala"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["University at Buffalo"],"species":["Homo Sapiens (human)"],"publication":["41529070 Gulla S, Sharma T, Gardner E, Li C, Purohit TA, Xue C, Colligan S, Shyam Sundar S, Yang B, Trostel SY, Capaldo B, Bard JE, Ogunbowale T, Jawadwala A, Ma M, Qu J, Karzai F, Pili R, Jarrard DF, Sowalsky AG, VanderWeele DJ, Adelaiye-Ogala R. MECOM Function Is Critical for AR-Driven Treatment-Resistant Prostate Cancer. Cancer Res. 2026 86(9):2143-2160 10.1158/0008-5472.can-25-1720"],"submitter_mail":["remiadel@buffalo.edu"],"submitter_affiliation":["University at Buffalo"],"submitter_country":["United States"],"pubmed_abstract":["Reprogramming of the androgen receptor (AR) cistrome is associated with prostate cancer progression, and advanced castration-resistant prostate cancers (CRPC) tend to rely on reprogrammed/noncanonical AR signaling that remains active under treatment with AR signaling inhibitors (ARSI). In this study, we identified ecotropic viral integration site 1 (EVI1), an oncogenic nuclear transcription factor (TF) encoded by MECOM, as an AR-recruited coactivator of noncanonical signaling. In prostate cancer, MECOM was exclusively overexpressed in both CRPC and enzalutamide-resistant CRPC and interacted with AR in the nucleus. MECOM depletion in prostate cancer cells decreased proliferation, altered cell survival transcriptional programs, and reduced the number of super-enhancers (SE), leading to a dynamic change in the SE landscape and a decrease in the expression of SE-regulated oncogenic TFs, along with increased proapoptotic signatures. Notably, cells overexpressing MECOM and its protein, EVI1, were susceptible to PARP inhibitors (PARPi) regardless of their DNA damage response or homologous recombination repair (HRR) gene mutation status. These insights reveal the crucial role of EVI1 in regulating cell survival within the context of an AR-reprogrammed chromatin landscape. More importantly, the findings suggest that MECOM overexpression may be another biomarker that could significantly broaden the use of PARPis beyond those with HRR gene mutations.<h4>Significance</h4>MECOM is a driver of androgen receptor inhibitor resistance in castrate-resistant prostate cancer that promotes susceptibility to PARP inhibition, positioning MECOM as a biomarker in patients without homologous recombination repair gene mutations."],"pubmed_title":["MECOM Function Is Critical for AR-Driven Treatment-Resistant Prostate Cancer."],"pubmed_authors":["Gulla Surendra S, Sharma Tej T, Gardner Ephraim E, Li Chennan C, Purohit Tanaya A TA, Xue Chao C, Colligan Sean S, Shyam Sundar Shreya S, Yang Bing B, Trostel Shana Y SY, Capaldo Brian B, Bard Jonathan E JE, Ogunbowale Tobilola T, Jawadwala Abbas A, Ma Min M, Qu Jun J, Karzai Fatima F, Pili Roberto R, Jarrard David F DF, Sowalsky Adam G AG, VanderWeele David J DJ, Adelaiye-Ogala Remi R"],"additional_accession":[]},"is_claimable":false,"name":"MECOM: A novel player in AR-driven Treatment Resistant Castration-Resistant Prostate Cancer","description":"Reprogramming of the androgen receptor (AR) cistrome is associated with disease progression, and advanced castrate-resistant prostate cancers (CRPC) tend to rely on a reprogrammed/non-canonical AR signaling that is addictive to AR signaling inhibitor (ARSI) resistance. We identified EVI1, an oncogenic nuclear transcription factor, EVI1 coded by MECOM, as a novel AR-recruited co-activator for non-canonical signaling. In prostate cancer, MECOM is exclusively overexpressed in CRPC and enzalutamide-resistant CRPC and interacts with AR in the nucleus. MECOM knockdown cells exhibited decreased proliferation, aberration of critical cell survival transcriptional programs, suppressed super-enhancer (SE) activity, and increased pro-apoptotic signatures. Intriguingly, MECOM overexpression is vulnerable to PARP inhibitors regardless of DDR or HRR gene mutation status. These insights uncover the mechanistic role of MECOM in AR reprogrammed cistrome for cell survival and its vulnerability. More importantly, this study suggests that MECOM overexpression may be another biomarker that could significantly broaden the use of PARP inhibitors beyond those with HRR gene mutations.","dates":{"publication":"2026-06-08","submission":"2025-03-28"},"accession":"PXD062331","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:108018","NEWT:377960","NEWT:1131","NEWT:35795","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:247480","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:1599","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:12215","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:2736291","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:294671","NEWT:376619","NEWT:1748418","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:4615","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:3760","NEWT:1584","NEWT:2086595","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:381198","NEWT:418106","NCBITaxon:12721","NEWT:166340","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:3357","NEWT:7719","NEWT:29073","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:2767846","NEWT:108061","NEWT:60711","NEWT:2020713","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:3349","NEWT:160621","NEWT:2502409","NEWT:212790","NEWT:110368","NEWT:1916073","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:468822","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:370038","NEWT:498211","NEWT:345076","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:200795","NEWT:342808","NEWT:2579791","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:260499","NEWT:410661","NEWT:329854","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:2649329","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:709964","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:156974","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:3715","NEWT:1538","NEWT:2065263","NEWT:199225","NEWT:177437","NEWT:717966","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:29022","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:52299","NEWT:1883426","NEWT:8165","NEWT:96794","NEWT:10401","NEWT:10886","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1955249","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:2714896","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:1608994","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:1122981","NEWT:2853422","NEWT:1122984","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:45972","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:2836","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:31345","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:141469","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:1922344","NEWT:108458","NEWT:5936","NEWT:85692","NEWT:321967","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:279010","NEWT:291146","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:415978","NEWT:235455","NEWT:1255228","NEWT:410289","NEWT:191701","NEWT:373153","NEWT:1640278","NEWT:9054","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:1380096","NEWT:28128","NEWT:470","NEWT:41122","NEWT:5911","NEWT:1328300","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:911022","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:717989","NEWT:33952","NEWT:1255232","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166314","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:1871049","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:3726","NEWT:906914","NEWT:81231006","NEWT:30455","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737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