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

• DOI: 10.1002/path.5281
• Publication Date: 2019-04-15T04:11:06Z
• Authors: Maren Voglstaetter; Andreas R Thomsen; Jerome Nouvel; Arend Koch; Paul Jank; Elena Grueso Navarro; Tanja Gainey‐Schl...; Richa Khanduri; Andrea Groß; Florian Rossner; Carina Blaue; Clemens M Franz; Marina Veil; Gerhard Puetz; Andreas Hippe; Jochen Dindorf; Jubin Kashef; Wilko Thiele; Bernhard Homey; Celine Greco; Claude Boucheix; Andreas Baur; Thalia Erbes; Cornelius F Waller; Marie Follo; Ghamartaj Hossein; Christine Sers; Jonathan Sleeman; Irina Nazarenko
• Keywords: 0301 basic medicine; 570; Tetraspanins; 610; Breast Neoplasms; Extracellular Vesicles; 03 medical and health sciences; Cell Line, Tumor; Brustkrebs; Biomarkers, Tumor; Animals; Humans; Neoplasm Metastasis; info:eu-repo/classification/ddc/570; biology; Carcinoma, Ductal, Breast; Cadherins; Life sciences; Original Papers; Rats; 3. Good health; Carcinoma, Lobular; Carcinoma, Intraductal, Noninfiltrating; Female; ddc:570; Signal Transduction

Abstract Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present first study on the expression function of breast cancer. protein was majority human primary lesions metastases brain, bone, lung, liver. In syngeneic rat model, + tumours formed multiple liver spleen metastases, while − exhibited significantly diminished ability to metastasise, indicating metastases. Addressing underlying molecular mechanisms, we discovered that can mediate up‐regulation E‐cadherin down‐regulation Twist, p120‐catenin, β‐catenin target genes accompanied by change cell phenotype, resembling mesenchymal–epithelial transition. Furthermore, cells enhanced cell–cell adhesion, motility, decreased sensitivity irradiation. As regulator content extracellular vesicles (EVs), mediated several‐fold increase EV number culture circulation tumour‐bearing animals. observed increased levels p120‐catenin these EVs; furthermore, were co‐immunoprecipitated, they may interact with each other. Altogether, our findings show presence lesion indicate its as behaviour release © 2019 The Authors. Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.