{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:59:59Z","timestamp":1792785599952,"version":"4.5.0"},"reference-count":51,"publisher":"Rockefeller University Press","issue":"1","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":199,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB841"],"award-info":[{"award-number":["SFB841"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB877"],"award-info":[{"award-number":["SFB877"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Technology Network"},{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["57315783"],"award-info":[{"award-number":["57315783"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002869","name":"Christian-Albrechts-University Kiel","doi-asserted-by":"publisher","award":["F358901"],"award-info":[{"award-number":["F358901"]}],"id":[{"id":"10.13039\/501100002869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010782","name":"Cluster of Excellence \u201cInflammation at Interfaces\u201d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010782","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["01EY1103"],"award-info":[{"award-number":["01EY1103"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,1,3]]},"abstract":"<jats:p>Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis. We show that TNFR1-dependent tumor cell\u2013induced endothelial cell death, tumor cell extravasation, and subsequent metastatic seeding is dependent on the activity of endothelial ADAM17. Moreover, we reveal that ADAM17-mediated TNFR1 ectodomain shedding and subsequent processing by the \u03b3-secretase complex is required for the induction of TNF-induced necroptosis. Consequently, genetic ablation of ADAM17 in endothelial cells as well as short-term pharmacological inhibition of ADAM17 prevents long-term metastases formation in the lung. Thus, our data identified ADAM17 as a novel essential regulator of necroptosis and as a new promising target for antimetastatic and advanced-stage cancer therapies.<\/jats:p>","DOI":"10.1084\/jem.20201039","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T02:21:53Z","timestamp":1635992513000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis"],"prefix":"10.1084","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5559-4326","authenticated-orcid":true,"given":"Julia","family":"Bolik","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-5859","authenticated-orcid":true,"given":"Freia","family":"Krause","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"},{"name":"Department of Biosciences, Paris-Lodron University Salzburg, Salzburg, Austria 17"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-639X","authenticated-orcid":true,"given":"Marija","family":"Stevanovic","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-8740","authenticated-orcid":true,"given":"Monja","family":"Gandra\u00df","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9556-6055","authenticated-orcid":true,"given":"Ilka","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2512-1741","authenticated-orcid":true,"given":"Sarah-Sophie","family":"Schacht","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-8097","authenticated-orcid":true,"given":"Eva","family":"Rieser","sequence":"additional","affiliation":[{"name":"Centre for Cell Death, Cancer and Inflammation, UCL Cancer Institute, University College London, London, United Kingdom 2"},{"name":"Institute for Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0751-1407","authenticated-orcid":true,"given":"Miryam","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-0365","authenticated-orcid":true,"given":"Neele","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6909-6096","authenticated-orcid":true,"given":"J\u00fcrgen","family":"Fritsch","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Christian-Albrechts-University Kiel, Kiel, Germany 4"},{"name":"Department of Infection Prevention and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1291-5673","authenticated-orcid":true,"given":"Rielana","family":"Wichert","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-6702","authenticated-orcid":true,"given":"Eithan","family":"Galun","sequence":"additional","affiliation":[{"name":"The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-8573","authenticated-orcid":true,"given":"Juri","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Christian-Albrechts-University Kiel, Kiel, Germany 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7881-9110","authenticated-orcid":true,"given":"Christian","family":"R\u00f6der","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cancer Research, University Medical Center Schleswig-Holstein, Kiel, Germany 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-0707","authenticated-orcid":true,"given":"Clemens","family":"Schafmayer","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Thoracic Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-8897","authenticated-orcid":true,"given":"Jan-Hendrik","family":"Egberts","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Thoracic Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5100-9916","authenticated-orcid":true,"given":"Christoph","family":"Becker-Pauly","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2637-7052","authenticated-orcid":true,"given":"Paul","family":"Saftig","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-1760","authenticated-orcid":true,"given":"Ralph","family":"Lucius","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Christian-Albrechts-University Kiel, Kiel, Germany 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2707-2923","authenticated-orcid":true,"given":"Wulf","family":"Schneider-Brachert","sequence":"additional","affiliation":[{"name":"Department of Infection Prevention and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4953-931X","authenticated-orcid":true,"given":"Roja","family":"Barikbin","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5668-5032","authenticated-orcid":true,"given":"Dieter","family":"Adam","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Christian-Albrechts-University Kiel, Kiel, Germany 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4217-3175","authenticated-orcid":true,"given":"Matthias","family":"Voss","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7696-1479","authenticated-orcid":true,"given":"Wolfgang","family":"Hitzl","sequence":"additional","affiliation":[{"name":"Research Office (Biostatistics), Paracelsus Medical University, Salzburg, Austria 11"},{"name":"Research Program for Experimental Ophthalmology and Glaucoma, Paracelsus Medical University, Salzburg, Austria 12"},{"name":"Department of Ophthalmology and Optometry, Paracelsus Medical University Salzburg, Salzburg, Austria 13"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-9256","authenticated-orcid":true,"given":"Achim","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Institutes for Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany 14"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-8094","authenticated-orcid":true,"given":"Boris","family":"Strilic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany 15"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5595-5515","authenticated-orcid":true,"given":"Irit","family":"Sagi","sequence":"additional","affiliation":[{"name":"Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel 16"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6312-4591","authenticated-orcid":true,"given":"Henning","family":"Walczak","sequence":"additional","affiliation":[{"name":"Centre for Cell Death, Cancer and Inflammation, UCL Cancer Institute, University College London, London, United Kingdom 2"},{"name":"Institute for Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7519-3279","authenticated-orcid":true,"given":"Stefan","family":"Rose-John","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-7495","authenticated-orcid":true,"given":"Dirk","family":"Schmidt-Arras","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany 1"},{"name":"Department of Biosciences, Paris-Lodron University Salzburg, Salzburg, Austria 17"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"2023072610275316100_bib1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190218","article-title":"Emerging paradigms in metastasis research","volume":"218","author":"Abdul Pari","year":"2021","journal-title":"J. Exp. Med."},{"key":"2023072610275316100_bib2","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1056\/NEJMoa1100721","article-title":"Inflammatory skin and bowel disease linked to ADAM17 deletion","volume":"365","author":"Blaydon","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2023072610275316100_bib3","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/nature13862","article-title":"Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis","volume":"515","author":"Bonapace","year":"2014","journal-title":"Nature."},{"key":"2023072610275316100_bib4","doi-asserted-by":"publisher","first-page":"32488","DOI":"10.1016\/S0021-9258(18)31661-2","article-title":"Structural requirements for inducible shedding of the p55 tumor necrosis factor receptor","volume":"269","author":"Brakebusch","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2023072610275316100_bib5","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/nri3834","article-title":"Regulation of tumour necrosis factor signalling: live or let die","volume":"15","author":"Brenner","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"2023072610275316100_bib6","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/cr.2016.87","article-title":"Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration","volume":"26","author":"Cai","year":"2016","journal-title":"Cell Res."},{"key":"2023072610275316100_bib7","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1084\/jem.20092366","article-title":"Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice","volume":"207","author":"Chalaris","year":"2010","journal-title":"J. Exp. Med."},{"key":"2023072610275316100_bib8","doi-asserted-by":"publisher","first-page":"5971","DOI":"10.1074\/jbc.M115.679076","article-title":"\u03b3-Secretase activity is required for regulated intramembrane proteolysis of tumor necrosis factor (TNF) receptor 1 and TNF-mediated pro-apoptotic signaling","volume":"291","author":"Chhibber-Goel","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2023072610275316100_bib9","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1023\/A:1008942828960","article-title":"Conditional gene targeting in macrophages and granulocytes using LysMcre mice","volume":"8","author":"Clausen","year":"1999","journal-title":"Transgenic Res."},{"key":"2023072610275316100_bib10","doi-asserted-by":"publisher","first-page":"12941","DOI":"10.18632\/oncotarget.24410","article-title":"The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis","volume":"9","author":"Fuchslocher Chico","year":"2018","journal-title":"Oncotarget."},{"key":"2023072610275316100_bib11","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/0092-8674(95)90192-2","article-title":"The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor","volume":"83","author":"Grell","year":"1995","journal-title":"Cell."},{"key":"2023072610275316100_bib12","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.20","article-title":"RIPK1\/RIPK3 promotes vascular permeability to allow TC extravasation independent of its necroptotic function","volume":"8","author":"H\u00e4nggi","year":"2017","journal-title":"Cell Death Dis."},{"key":"2023072610275316100_bib13","volume-title":"Statistics: Methods and Applications.","author":"Hill","year":"2006"},{"key":"2023072610275316100_bib14","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.4049\/jimmunol.179.5.2686","article-title":"Cutting edge: TNF-alpha-converting enzyme (TACE\/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock","volume":"179","author":"Horiuchi","year":"2007","journal-title":"J. Immunol."},{"key":"2023072610275316100_bib15","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41419-019-1735-6","article-title":"Discovery of potent necroptosis inhibitors targeting RIPK1 kinase activity for the treatment of inflammatory disorder and cancer metastasis","volume":"10","author":"Hou","year":"2019","journal-title":"Cell Death Dis."},{"key":"2023072610275316100_bib16","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1038\/nmeth.2172","article-title":"TGF\u03b1 shedding assay: an accurate and versatile method for detecting GPCR activation","volume":"9","author":"Inoue","year":"2012","journal-title":"Nat. Methods."},{"key":"2023072610275316100_bib17","doi-asserted-by":"publisher","first-page":"4944","DOI":"10.1038\/ncomms5944","article-title":"TNFR1 mediates TNF-\u03b1-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling","volume":"5","author":"Ji","year":"2014","journal-title":"Nat. Commun."},{"key":"2023072610275316100_bib18","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nature07623","article-title":"Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis","volume":"457","author":"Kim","year":"2009","journal-title":"Nature."},{"key":"2023072610275316100_bib19","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1038\/s41556-018-0229-6","article-title":"TBK1 and IKK\u03b5 prevent TNF-induced cell death by RIPK1 phosphorylation","volume":"20","author":"Lafont","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"2023072610275316100_bib20","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/nrclinonc.2016.128","article-title":"Does the mobilization of circulating tumour cells during cancer therapy cause metastasis?","volume":"14","author":"Martin","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2023072610275316100_bib21","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1056\/NEJM199707173370301","article-title":"Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein","volume":"337","author":"Moreland","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"2023072610275316100_bib22","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/nrc2459","article-title":"The ADAMs: signalling scissors in the tumour microenvironment","volume":"8","author":"Murphy","year":"2008","journal-title":"Nat. Rev. Cancer."},{"key":"2023072610275316100_bib23","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1146\/annurev-biophys-083012-130338","article-title":"Molecular basis of NF-\u03baB signaling","volume":"42","author":"Napetschnig","year":"2013","journal-title":"Annu. Rev. Biophys."},{"issue":"4","key":"2023072610275316100_bib51","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1128\/MCB.24.4.1464-1469.2004","article-title":"Kinase RIP3 is dispensable for normal NF-kappa Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4","volume":"24","author":"Newton","year":"2004","journal-title":"Mol. Cell Biol"},{"key":"2023072610275316100_bib24","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1161\/ATVBAHA.116.308682","article-title":"Adam17 deficiency promotes atherosclerosis by enhanced TNFR2 signaling in mice","volume":"37","author":"Nicolaou","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2023072610275316100_bib25","doi-asserted-by":"publisher","DOI":"10.3390\/cells8030209","article-title":"Presenilins and \u03b3-secretase in membrane proteostasis","volume":"8","author":"Oikawa","year":"2019","journal-title":"Cells."},{"key":"2023072610275316100_bib26","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1016\/j.cell.2019.02.001","article-title":"Higher-order clustering of the transmembrane anchor of DR5 drives signaling","volume":"176","author":"Pan","year":"2019","journal-title":"Cell."},{"key":"2023072610275316100_bib27","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41418-019-0347-0","article-title":"RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases","volume":"27","author":"Patel","year":"2020","journal-title":"Cell Death Differ."},{"key":"2023072610275316100_bib28","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.it.2019.03.006","article-title":"Cell death and inflammation - a vital but dangerous liaison","volume":"40","author":"Peltzer","year":"2019","journal-title":"Trends Immunol."},{"issue":"1","key":"2023072610275316100_bib50","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.celrep.2014.08.066","article-title":"HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death","volume":"9","author":"Peltzer","year":"2014","journal-title":"Cell Rep"},{"key":"2023072610275316100_bib29","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1126\/science.282.5392.1281","article-title":"An essential role for ectodomain shedding in mammalian development","volume":"282","author":"Peschon","year":"1998","journal-title":"Science."},{"key":"2023072610275316100_bib30","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/0092-8674(93)90134-C","article-title":"Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection","volume":"73","author":"Pfeffer","year":"1993","journal-title":"Cell."},{"key":"2023072610275316100_bib31","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.semcdb.2008.11.002","article-title":"The \u201ca disintegrin and metalloprotease\u201d (ADAM) family of sheddases: physiological and cellular functions","volume":"20","author":"Reiss","year":"2009","journal-title":"Semin. Cell Dev. Biol."},{"key":"2023072610275316100_bib32","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1038\/nrc3628","article-title":"Crossing the endothelial barrier during metastasis","volume":"13","author":"Reymond","year":"2013","journal-title":"Nat. Rev. Cancer."},{"key":"2023072610275316100_bib49","doi-asserted-by":"publisher","first-page":"25550","DOI":"10.1038\/srep25550","article-title":"Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17","volume":"6","author":"Riethmueller","year":"2016","journal-title":"Sci. Rep"},{"key":"2023072610275316100_bib33","author":"RStudio Team","year":"2020"},{"key":"2023072610275316100_bib34","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.it.2011.05.005","article-title":"ADAM17: a molecular switch to control inflammation and tissue regeneration","volume":"32","author":"Scheller","year":"2011","journal-title":"Trends Immunol."},{"key":"2023072610275316100_bib35","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1084\/jem.20171696","article-title":"ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling","volume":"215","author":"Schmidt","year":"2018","journal-title":"J. Exp. Med."},{"key":"2023072610275316100_bib36","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.ccr.2013.05.008","article-title":"Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor","volume":"24","author":"Schumacher","year":"2013","journal-title":"Cancer Cell."},{"key":"2023072610275316100_bib37","doi-asserted-by":"publisher","first-page":"5680","DOI":"10.1182\/blood-2008-08-174508","article-title":"DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries","volume":"113","author":"S\u00f6rensen","year":"2009","journal-title":"Blood."},{"key":"2023072610275316100_bib38","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.ccell.2017.07.001","article-title":"Intravascular survival and extravasation of TCs","volume":"32","author":"Strilic","year":"2017","journal-title":"Cancer Cell."},{"key":"2023072610275316100_bib39","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nature19076","article-title":"Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis","volume":"536","author":"Strilic","year":"2016","journal-title":"Nature."},{"key":"2023072610275316100_bib40","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aax1194","article-title":"iRhom2 inhibits bile duct obstruction-induced liver fibrosis","volume":"12","author":"Sundaram","year":"2019","journal-title":"Sci. Signal."},{"issue":"13","key":"2023072610275316100_bib48","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1093\/hmg\/ddh151","article-title":"Partial loss of presenilins causes seborrheic keratosis and autoimmune disease in mice","volume":"13","author":"Tournoy","year":"2004","journal-title":"Hum. Mol. Genet"},{"key":"2023072610275316100_bib41","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aao4910","article-title":"Structural principles of tumor necrosis factor superfamily signaling","volume":"11","author":"Vanamee","year":"2018","journal-title":"Sci. Signal."},{"key":"2023072610275316100_bib42","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030764","article-title":"On the TRAIL of better therapies: understanding TNFRSF structure-function","volume":"9","author":"Vanamee","year":"2020","journal-title":"Cells."},{"key":"2023072610275316100_bib43","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ccr.2012.05.023","article-title":"Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway","volume":"22","author":"Wolf","year":"2012","journal-title":"Cancer Cell."},{"key":"2023072610275316100_bib44","doi-asserted-by":"publisher","first-page":"12135","DOI":"10.1074\/jbc.M114.624072","article-title":"The functional maturation of a disintegrin and metalloproteinase (ADAM) 9, 10, and 17 requires processing at a newly identified proprotein convertase (PC) cleavage site","volume":"290","author":"Wong","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2023072610275316100_bib45","doi-asserted-by":"publisher","first-page":"35598","DOI":"10.1038\/srep35598","article-title":"Harnessing the natural inhibitory domain to control TNF\u03b1 converting enzyme (TACE) activity in vivo","volume":"6","author":"Wong","year":"2016","journal-title":"Sci. Rep."},{"key":"2023072610275316100_bib46","doi-asserted-by":"publisher","first-page":"ra34","DOI":"10.1126\/scisignal.2002689","article-title":"TACE activation by MAPK-mediated regulation of cell surface dimerization and TIMP3 association","volume":"5","author":"Xu","year":"2012","journal-title":"Sci. Signal."},{"key":"2023072610275316100_bib47","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1038\/s41418-018-0271-8","article-title":"TAK1 regulates endothelial cell necroptosis and tumor metastasis","volume":"26","author":"Yang","year":"2019","journal-title":"Cell Death Differ."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20201039\/1767564\/jem_20201039.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20201039\/1767564\/jem_20201039.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T06:34:43Z","timestamp":1690353283000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/219\/1\/e20201039\/212921\/Inhibition-of-ADAM17-impairs-endothelial-cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,17]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,3]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20201039","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,17]]},"article-number":"e20201039"}}