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Tspan8 is expressed in breast cancer and regulates E-cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Voglstaetter, M.; Thomsen, A. R.; Nouvel, J.; Koch, A.; Jank, P.; Navarro, E. G.; Gainey-Schleicher, T.; Khanduri, R.; Groß, A.; Rossner, F.; Blaue, C.; Franz, C. M.; Veil, M.; Puetz, G.; Hippe, A.; Dindorf, J.; Kashef, J.; Thiele, W.; Homey, B.; Greco, C.; ... mehr

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$^{+}$ tumours formed multiple liver and spleen metastases, while Tspan8$^{-}$ 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‐regulation of E‐cadherin and down‐regulation of Twist, p120‐catenin, and β‐catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8$^{+}$ cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several‐fold increase in EV number in cell culture and the circulation of tumour‐bearing animals. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000096403
Veröffentlicht am 09.08.2019
DOI: 10.1002/path.5281
Zitationen: 7
Web of Science
Zitationen: 5
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Institut für Photonenforschung und Synchrotronstrahlung (IPS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2019
Sprache Englisch
Identifikator ISSN: 0022-3417, 0368-3494, 1096-9896, 1555-2039
KITopen-ID: 1000096403
HGF-Programm 47.01.01 (POF III, LK 01)
Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in The journal of pathology
Band 248
Heft 4
Seiten 421-437
Vorab online veröffentlicht am 14.04.2019
Nachgewiesen in Scopus
Web of Science
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