guest ::
| Home > Publications Database > A high-content screen for small-molecule regulators of epithelial cell-adhesion molecule (EpCAM) cleavage yields a robust inhibitor. > print |
| Home > Publications Database > A high-content screen for small-molecule regulators of epithelial cell-adhesion molecule (EpCAM) cleavage yields a robust inhibitor. > print |
| 001 | 140001 | ||
| 005 | 20240321220727.0 | ||
| 024 | 7 | _ | |a 10.1074/jbc.RA118.002776 |2 doi |
| 024 | 7 | _ | |a pmid:29700109 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC5995519 |2 pmc |
| 024 | 7 | _ | |a 0021-9258 |2 ISSN |
| 024 | 7 | _ | |a 1067-8816 |2 ISSN |
| 024 | 7 | _ | |a 1083-351X |2 ISSN |
| 024 | 7 | _ | |a altmetric:39598280 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-06323 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 540 |
| 100 | 1 | _ | |a Tretter, Jana Ylva |b 0 |
| 245 | _ | _ | |a A high-content screen for small-molecule regulators of epithelial cell-adhesion molecule (EpCAM) cleavage yields a robust inhibitor. |
| 260 | _ | _ | |a Bethesda, Md. |c 2018 |b Soc.60645 |
| 264 | _ | 1 | |3 online |2 Crossref |b American Society for Biochemistry & Molecular Biology (ASBMB) |c 2018-04-26 |
| 264 | _ | 1 | |3 print |2 Crossref |b American Society for Biochemistry & Molecular Biology (ASBMB) |c 2018-06-08 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1588085759_27570 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Epithelial cell-adhesion molecule (EpCAM) is a transmembrane protein that regulates cell cycle progression and differentiation and is overexpressed in many carcinomas. The EpCAM-induced mitogenic cascade is activated via regulated intramembrane proteolysis (RIP) of EpCAM by ADAM and γ-secretases, generating the signaling-active intracellular domain EpICD. Because of its expression pattern and molecular function, EpCAM is a valuable target in prognostic and therapeutic approaches for various carcinomas. So far, several immunotherapeutic strategies have targeted the extracellular domain of EpCAM. However, targeting the intracellular signaling cascade of EpCAM holds promise for specifically interfering with EpCAM's proliferation-stimulating signaling cascade. Here, using a yellow fluorescence protein-tagged version of the C-terminal fragment of EpCAM, we established a high-content screening (HCS) of a small-molecule compound library (n = 27,280) and characterized validated hits that target EpCAM signaling. In total, 128 potential inhibitors were initially identified, of which one compound with robust inhibitory effects on RIP of EpCAM was analyzed in greater detail. In summary, our study demonstrates that the development of an HCS for small-molecule inhibitors of the EpCAM signaling pathway is feasible. We propose that this approach may also be useful for identifying chemical compounds targeting other disorders involving membrane cleavage-dependent signaling pathways. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Epithelial Cell Adhesion Molecule |2 NLM Chemicals |
| 650 | _ | 7 | |a Small Molecule Libraries |2 NLM Chemicals |
| 650 | _ | 2 | |a Cell Proliferation: drug effects |2 MeSH |
| 650 | _ | 2 | |a Drug Evaluation, Preclinical: methods |2 MeSH |
| 650 | _ | 2 | |a Epithelial Cell Adhesion Molecule: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a Epithelial Cell Adhesion Molecule: metabolism |2 MeSH |
| 650 | _ | 2 | |a HEK293 Cells |2 MeSH |
| 650 | _ | 2 | |a High-Throughput Screening Assays: methods |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Signal Transduction: drug effects |2 MeSH |
| 650 | _ | 2 | |a Small Molecule Libraries: chemistry |2 MeSH |
| 650 | _ | 2 | |a Small Molecule Libraries: pharmacology |2 MeSH |
| 650 | _ | 2 | |a Transcription, Genetic: drug effects |2 MeSH |
| 700 | 1 | _ | |a Schorpp, Kenji |b 1 |
| 700 | 1 | _ | |a Luxenburger, Elke |b 2 |
| 700 | 1 | _ | |a Trambauer, Johannes |b 3 |
| 700 | 1 | _ | |a Steiner, Harald |0 P:(DE-2719)2000023 |b 4 |u dzne |
| 700 | 1 | _ | |a Hadian, Kamyar |b 5 |
| 700 | 1 | _ | |a Gires, Olivier |0 P:(DE-HGF)0 |b 6 |e Corresponding author |
| 700 | 1 | _ | |a Niessing, Dierk |b 7 |
| 773 | 1 | 8 | |a 10.1074/jbc.ra118.002776 |b : American Society for Biochemistry & Molecular Biology (ASBMB), 2018-04-26 |n 23 |p 8994-9005 |3 journal-article |2 Crossref |t Journal of Biological Chemistry |v 293 |y 2018 |x 0021-9258 |
| 773 | _ | _ | |a 10.1074/jbc.RA118.002776 |g Vol. 293, no. 23, p. 8994 - 9005 |0 PERI:(DE-600)1474604-9 |n 23 |q 293:23<8994 - 9005 |p 8994-9005 |t The journal of biological chemistry |v 293 |y 2018 |x 0021-9258 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995519 |
| 909 | C | O | |o oai:pub.dzne.de:140001 |p VDB |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 4 |6 P:(DE-2719)2000023 |
| 913 | 1 | _ | |a DE-HGF |b Forschungsbereich Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-342 |2 G:(DE-HGF)POF3-300 |v Disease Mechanisms and Model Systems |x 0 |
| 914 | 1 | _ | |y 2018 |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b J BIOL CHEM : 2019 |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0320 |2 StatID |b PubMed Central |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |d 2021-05-04 |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |d 2021-05-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2021-05-04 |
| 915 | _ | _ | |a IF < 5 |0 StatID:(DE-HGF)9900 |2 StatID |d 2021-05-04 |
| 920 | 1 | _ | |0 I:(DE-2719)1110000-1 |k AG Steiner |l Biochemistry of γ-Secretase |x 0 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-2719)1110000-1 |
| 980 | _ | _ | |a UNRESTRICTED |
| 999 | C | 5 | |a 10.1083/jcb.125.2.437 |9 -- missing cx lookup -- |2 Crossref |o 10.1083/jcb.125.2.437 |
| 999 | C | 5 | |a 10.1073/pnas.91.13.5833 |9 -- missing cx lookup -- |2 Crossref |o 10.1073/pnas.91.13.5833 |
| 999 | C | 5 | |a 10.1073/pnas.86.1.27 |9 -- missing cx lookup -- |2 Crossref |o 10.1073/pnas.86.1.27 |
| 999 | C | 5 | |a 10.1073/pnas.87.9.3542 |9 -- missing cx lookup -- |2 Crossref |o 10.1073/pnas.87.9.3542 |
| 999 | C | 5 | |a 10.1152/ajpgi.00069.2014 |9 -- missing cx lookup -- |2 Crossref |o 10.1152/ajpgi.00069.2014 |
| 999 | C | 5 | |2 Crossref |o |
| 999 | C | 5 | |a 10.1038/sj.bjc.6603494 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/sj.bjc.6603494 |
| 999 | C | 5 | |a 10.3109/15419069409004452 |9 -- missing cx lookup -- |2 Crossref |o 10.3109/15419069409004452 |
| 999 | C | 5 | |a 10.1038/sj.onc.1207610 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/sj.onc.1207610 |
| 999 | C | 5 | |a 10.1038/ncb1824 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/ncb1824 |
| 999 | C | 5 | |a 10.1158/1541-7786.MCR-12-0518 |9 -- missing cx lookup -- |2 Crossref |o 10.1158/1541-7786.MCR-12-0518 |
| 999 | C | 5 | |a 10.1074/jbc.M109.077081 |9 -- missing cx lookup -- |2 Crossref |o 10.1074/jbc.M109.077081 |
| 999 | C | 5 | |a 10.1038/onc.2016.504 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/onc.2016.504 |
| 999 | C | 5 | |a 10.1038/onc.2012.75 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/onc.2012.75 |
| 999 | C | 5 | |a 10.1038/srep41852 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/srep41852 |
| 999 | C | 5 | |a 10.1038/s41598-018-20131-8 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/s41598-018-20131-8 |
| 999 | C | 5 | |a 10.1002/ijc.10270 |9 -- missing cx lookup -- |2 Crossref |o 10.1002/ijc.10270 |
| 999 | C | 5 | |a 10.1023/B:BREA.0000036787.59816.01 |9 -- missing cx lookup -- |2 Crossref |o 10.1023/B:BREA.0000036787.59816.01 |
| 999 | C | 5 | |a 10.2353/ajpath.2007.070152 |9 -- missing cx lookup -- |2 Crossref |o 10.2353/ajpath.2007.070152 |
| 999 | C | 5 | |a 10.1002/stem.97 |9 -- missing cx lookup -- |2 Crossref |o 10.1002/stem.97 |
| 999 | C | 5 | |a 10.1002/stem.221 |9 -- missing cx lookup -- |2 Crossref |o 10.1002/stem.221 |
| 999 | C | 5 | |a 10.1002/jcp.26286 |9 -- missing cx lookup -- |2 Crossref |o 10.1002/jcp.26286 |
| 999 | C | 5 | |a 10.1084/jem.20061603 |9 -- missing cx lookup -- |2 Crossref |o 10.1084/jem.20061603 |
| 999 | C | 5 | |a 10.1007/s001099900038 |9 -- missing cx lookup -- |2 Crossref |o 10.1007/s001099900038 |
| 999 | C | 5 | |a 10.1016/j.humpath.2003.08.026 |9 -- missing cx lookup -- |2 Crossref |o 10.1016/j.humpath.2003.08.026 |
| 999 | C | 5 | |a 10.1038/nrc2521-c2, 10.1038/nrc2521-c1, 10.1038/nrc2499-c2, 10.1038/nrc2499-c1 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/nrc2521-c2, 10.1038/nrc2521-c1, 10.1038/nrc2499-c2, 10.1038/nrc2499-c1 |
| 999 | C | 5 | |a 10.1016/j.gene.2011.04.005 |9 -- missing cx lookup -- |2 Crossref |o 10.1016/j.gene.2011.04.005 |
| 999 | C | 5 | |a 10.1038/modpathol.3800733 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/modpathol.3800733 |
| 999 | C | 5 | |a 10.1016/j.oraloncology.2006.10.010 |9 -- missing cx lookup -- |2 Crossref |o 10.1016/j.oraloncology.2006.10.010 |
| 999 | C | 5 | |a 10.1186/1471-2407-10-331 |9 -- missing cx lookup -- |2 Crossref |o 10.1186/1471-2407-10-331 |
| 999 | C | 5 | |a 10.1371/journal.pone.0014130 |9 -- missing cx lookup -- |2 Crossref |o 10.1371/journal.pone.0014130 |
| 999 | C | 5 | |a 10.1136/jcp.2007.049460 |9 -- missing cx lookup -- |2 Crossref |o 10.1136/jcp.2007.049460 |
| 999 | C | 5 | |a 10.1136/jcp.2006.037333 |9 -- missing cx lookup -- |2 Crossref |o 10.1136/jcp.2006.037333 |
| 999 | C | 5 | |a 10.1016/j.cell.2009.11.025 |9 -- missing cx lookup -- |2 Crossref |o 10.1016/j.cell.2009.11.025 |
| 999 | C | 5 | |a 10.1038/bjc.2014.366 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/bjc.2014.366 |
| 999 | C | 5 | |a 10.1242/dev.091538 |9 -- missing cx lookup -- |2 Crossref |o 10.1242/dev.091538 |
| 999 | C | 5 | |a 10.1093/carcin/bgq187 |9 -- missing cx lookup -- |2 Crossref |o 10.1093/carcin/bgq187 |
| 999 | C | 5 | |a 10.1158/1078-0432.CCR-03-0528 |9 -- missing cx lookup -- |2 Crossref |o 10.1158/1078-0432.CCR-03-0528 |
| 999 | C | 5 | |a 10.3892/or.2016.4789 |9 -- missing cx lookup -- |2 Crossref |o 10.3892/or.2016.4789 |
| 999 | C | 5 | |a 10.1097/01.pas.0000.146028.70868.7a |9 -- missing cx lookup -- |2 Crossref |o 10.1097/01.pas.0000.146028.70868.7a |
| 999 | C | 5 | |a 10.1158/0008-5472.CAN-16-0842 |9 -- missing cx lookup -- |2 Crossref |o 10.1158/0008-5472.CAN-16-0842 |
| 999 | C | 5 | |a 10.1007/s00432-009-0569-5 |9 -- missing cx lookup -- |2 Crossref |o 10.1007/s00432-009-0569-5 |
| 999 | C | 5 | |a 10.1158/0008-5472.CAN-09-0654 |9 -- missing cx lookup -- |2 Crossref |o 10.1158/0008-5472.CAN-09-0654 |
| 999 | C | 5 | |y 1989 |2 Crossref |o Strnad 1989 |
| 999 | C | 5 | |a 10.1074/jbc.M008839200 |9 -- missing cx lookup -- |2 Crossref |o 10.1074/jbc.M008839200 |
| 999 | C | 5 | |a 10.1111/j.1432-1033.1996.0125h.x |9 -- missing cx lookup -- |2 Crossref |o 10.1111/j.1432-1033.1996.0125h.x |
| 999 | C | 5 | |a 10.1186/1471-2407-9-402 |9 -- missing cx lookup -- |2 Crossref |o 10.1186/1471-2407-9-402 |
| 999 | C | 5 | |a 10.1016/j.mam.2008.08.001 |9 -- missing cx lookup -- |2 Crossref |o 10.1016/j.mam.2008.08.001 |
| 999 | C | 5 | |a 10.1074/jbc.M115.662700 |9 -- missing cx lookup -- |2 Crossref |o 10.1074/jbc.M115.662700 |
| 999 | C | 5 | |a 10.1038/sj.onc.1210057 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/sj.onc.1210057 |
| 999 | C | 5 | |a 10.4161/cam.18953 |9 -- missing cx lookup -- |2 Crossref |o 10.4161/cam.18953 |
| 999 | C | 5 | |a 10.1038/sj.bjc.6604725 |9 -- missing cx lookup -- |2 Crossref |o 10.1038/sj.bjc.6604725 |
| 999 | C | 5 | |a 10.1186/1475-2867-10-44 |9 -- missing cx lookup -- |2 Crossref |o 10.1186/1475-2867-10-44 |
| 999 | C | 5 | |a 10.1177/002215540104900711 |9 -- missing cx lookup -- |2 Crossref |o 10.1177/002215540104900711 |
| 999 | C | 5 | |a 10.1158/1078-0432.CCR-11-2767 |9 -- missing cx lookup -- |2 Crossref |o 10.1158/1078-0432.CCR-11-2767 |
| 999 | C | 5 | |a 10.1097/CJI.0b013e3181826d89 |9 -- missing cx lookup -- |2 Crossref |o 10.1097/CJI.0b013e3181826d89 |
| 999 | C | 5 | |a 10.1007/s11523-013-0290-9 |9 -- missing cx lookup -- |2 Crossref |o 10.1007/s11523-013-0290-9 |
| 999 | C | 5 | |a 10.4161/mabs.28207 |9 -- missing cx lookup -- |2 Crossref |o 10.4161/mabs.28207 |
| 999 | C | 5 | |a 10.18632/oncotarget.12073 |9 -- missing cx lookup -- |2 Crossref |o 10.18632/oncotarget.12073 |
| 999 | C | 5 | |a 10.1016/S0140-6736(82)91811-6 |9 -- missing cx lookup -- |2 Crossref |o 10.1016/S0140-6736(82)91811-6 |
| 999 | C | 5 | |y 1984 |2 Crossref |o Sears 1984 |
| 999 | C | 5 | |a 10.1200/JCO.2008.18.5710 |9 -- missing cx lookup -- |2 Crossref |o 10.1200/JCO.2008.18.5710 |
| 999 | C | 5 | |a 10.1200/JCO.2008.20.6284 |9 -- missing cx lookup -- |2 Crossref |o 10.1200/JCO.2008.20.6284 |
| 999 | C | 5 | |a 10.4161/mabs.2.2.11221 |9 -- missing cx lookup -- |2 Crossref |o 10.4161/mabs.2.2.11221 |
| 999 | C | 5 | |a 10.18632/oncotarget.4453 |9 -- missing cx lookup -- |2 Crossref |o 10.18632/oncotarget.4453 |
| 999 | C | 5 | |a 10.1159/000343863 |9 -- missing cx lookup -- |2 Crossref |o 10.1159/000343863 |
| 999 | C | 5 | |a 10.1371/journal.pone.0071836 |9 -- missing cx lookup -- |2 Crossref |o 10.1371/journal.pone.0071836 |
| 999 | C | 5 | |a 10.1093/embo-reports/kve180 |9 -- missing cx lookup -- |2 Crossref |o 10.1093/embo-reports/kve180 |
| 999 | C | 5 | |a 10.1093/nar/29.9.e45 |9 -- missing cx lookup -- |2 Crossref |o 10.1093/nar/29.9.e45 |
| 999 | C | 5 | |a 10.1177/108705719900400206 |9 -- missing cx lookup -- |2 Crossref |o 10.1177/108705719900400206 |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|