{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:41:55Z","timestamp":1790509315450,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T00:00:00Z","timestamp":1560816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["NA\u2010870\/1\u20101"],"award-info":[{"award-number":["NA\u2010870\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002714","name":"University of Freiburg","doi-asserted-by":"publisher","award":["3095170002"],"award-info":[{"award-number":["3095170002"]}],"id":[{"id":"10.13039\/501100002714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8\n                    <jats:sup>+<\/jats:sup>\n                    tumours formed multiple liver and spleen metastases, while Tspan8\n                    <jats:sup>\u2212<\/jats:sup>\n                    tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up\u2010regulation of E\u2010cadherin and down\u2010regulation of Twist, p120\u2010catenin, and \u03b2\u2010catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal\u2013epithelial transition. Furthermore, Tspan8\n                    <jats:sup>+<\/jats:sup>\n                    cells exhibited enhanced cell\u2013cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several\u2010fold increase in EV number in cell culture and the circulation of tumour\u2010bearing animals. We observed increased protein levels of E\u2010cadherin and p120\u2010catenin in these EVs; furthermore, Tspan8 and p120\u2010catenin were co\u2010immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. \u00a9 2019 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5281","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T00:11:06Z","timestamp":1555287066000},"page":"421-437","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Tspan8 is expressed in breast cancer and regulates E\u2010cadherin\/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles"],"prefix":"10.1002","volume":"248","author":[{"given":"Maren","family":"Voglstaetter","sequence":"first","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas R","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Medical Center, University of Freiburg  Freiburg im Breisgau Germany"},{"name":"German Cancer Consortium (DKTK) Partner Site Freiburg and German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Nouvel","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"},{"name":"Institute of Toxicology and Genetics, Karlsruhe Institute of Technology  Karlsruhe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arend","family":"Koch","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Jank","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Grueso","family":"Navarro","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Gainey\u2010Schleicher","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Khanduri","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gro\u00df","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Rossner","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Blaue","sequence":"additional","affiliation":[{"name":"DFG\u2010Center for Functional Nanostructures Karlsruhe Institute of Technology  Karlsruhe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens M","family":"Franz","sequence":"additional","affiliation":[{"name":"DFG\u2010Center for Functional Nanostructures Karlsruhe Institute of Technology  Karlsruhe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Veil","sequence":"additional","affiliation":[{"name":"Institute of Toxicology and Genetics, Karlsruhe Institute of Technology  Karlsruhe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Puetz","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine University of Freiburg  Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hippe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Faculty University of D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Dindorf","sequence":"additional","affiliation":[{"name":"Institute of Toxicology and Genetics, Karlsruhe Institute of Technology  Karlsruhe Germany"},{"name":"Department of Dermatology University Hospital Erlangen  Erlangen Germany"},{"name":"Translational Research Center Friedrich\u2010Alexander\u2010University of Erlangen\u2010Nuernberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jubin","family":"Kashef","sequence":"additional","affiliation":[{"name":"Institute for Photon Science and Synchrotron Radiation, Karlsruhe Institute of Technology (KIT)  Eggenstein\u2010Leopoldshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilko","family":"Thiele","sequence":"additional","affiliation":[{"name":"Medical Faculty University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Homey","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Faculty University of D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Greco","sequence":"additional","affiliation":[{"name":"UMR\u2010S935, Inserm Universit\u00e9 Paris Sud, Universit\u00e9 Paris Saclay  Villejuif France"},{"name":"Department of Pain Management and Palliative Care Necker Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Boucheix","sequence":"additional","affiliation":[{"name":"UMR\u2010S935, Inserm Universit\u00e9 Paris Sud, Universit\u00e9 Paris Saclay  Villejuif France"},{"name":"Department of Pain Management and Palliative Care Necker Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Baur","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital Erlangen  Erlangen Germany"},{"name":"Translational Research Center Friedrich\u2010Alexander\u2010University of Erlangen\u2010Nuernberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thalia","family":"Erbes","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius F","family":"Waller","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Follo","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Medical Center University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghamartaj","family":"Hossein","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"},{"name":"Department of Animal Physiology, Laboratory of Developmental Biology University of Tehran  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sers","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Sleeman","sequence":"additional","affiliation":[{"name":"Institute of Toxicology and Genetics, Karlsruhe Institute of Technology  Karlsruhe Germany"},{"name":"Medical Faculty University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2633-1161","authenticated-orcid":false,"given":"Irina","family":"Nazarenko","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Hospital Epidemiology; Medical Center \u2010 University of Freiburg Faculty of Medicine, University of Freiburg  Freiburg Germany"},{"name":"German Cancer Consortium (DKTK) Partner Site Freiburg and German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39104"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3265"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15748"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16064"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.05.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-179"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.154906"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.1.267"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2069"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00183-0"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605994"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.01.128"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2470"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4482"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2016-0126"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.520"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.11.031"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3471"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v3.26913"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15787"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.18457"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.8.1486"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2010.04.061"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(83)90208-2"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-05-1026"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-09-0777"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7LC00832E"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.02.027"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.08.005"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.08.009"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-015-9739-9"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1748-717X-5-82"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2898"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092317"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.09.012"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2753"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3169"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.6"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2017.00034"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-9-86"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12624"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4409"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.11.009"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1754"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2017.11"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.219"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253\u2010018\u20100522\u20105"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2949"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.10.002"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13321"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2006.00490.x"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2779"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2622"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3640"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2543"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00760"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16035363"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.064618"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2274-5"},{"key":"e_1_2_7_62_1","article-title":"Integrin \u03b16\/Akt\/Erk signaling is essential for human breast cancer resistance to radiotherapy","volume":"6","author":"Hu T","year":"2016","journal-title":"Sci Rep"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.5281","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5281","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5281","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:40:30Z","timestamp":1760953230000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,18]]},"references-count":61,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/path.5281"],"URL":"https:\/\/doi.org\/10.1002\/path.5281","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,18]]},"assertion":[{"value":"2018-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}