> Details

Cappelletto, Ambra; Alfì, Edoardo; Volf, Nina; Vu, Thi Van Anh; Bortolotti, Francesca; Ciucci, Giulio; Vodret, Simone; Fantuz, Marco; Perin, Martina; Colliva, Andrea; Rozzi, Giacomo; Rossi, Matilde; Ruozi, Giulia; Zentilin, Lorena; Vuerich, Roman; Borin, Daniele; Lapasin, Romano; Piazza, Silvano; Chiesa, Mattia; Lorizio, Daniela; Triboli, Luca; Kumar, Sandeep; Morello, Gaia; Tripodo, Claudio; [...]

EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening
  • Contributor: Cappelletto, Ambra; Alfì, Edoardo; Volf, Nina; Vu, Thi Van Anh; Bortolotti, Francesca; Ciucci, Giulio; Vodret, Simone; Fantuz, Marco; Perin, Martina; Colliva, Andrea; Rozzi, Giacomo; Rossi, Matilde; Ruozi, Giulia; Zentilin, Lorena; Vuerich, Roman; Borin, Daniele; Lapasin, Romano; Piazza, Silvano; Chiesa, Mattia; Lorizio, Daniela; Triboli, Luca; Kumar, Sandeep; Morello, Gaia; Tripodo, Claudio; [...]
  • Published: Springer Science and Business Media LLC, 2024
  • Published in: Journal of Experimental & Clinical Cancer Research, 43 (2024) 1
  • Language: English
  • DOI: 10.1186/s13046-023-02942-4
  • ISSN: 1756-9966
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: Abstract Background New drugs to tackle the next pathway or mutation fueling cancer are constantly proposed, but 97% of them are doomed to fail in clinical trials, largely because they are identified by cellular or in silico screens that cannot predict their in vivo effect. Methods We screened an Adeno-Associated Vector secretome library (> 1000 clones) directly in vivo in a mouse model of cancer and validated the therapeutic effect of the first hit, EMID2, in both orthotopic and genetic models of lung and pancreatic cancer. Results EMID2 overexpression inhibited both tumor growth and metastatic dissemination, consistent with prolonged survival of patients with high levels of EMID2 expression in the most aggressive human cancers. Mechanistically, EMID2 inhibited TGFβ maturation and activation of cancer-associated fibroblasts, resulting in more elastic ECM and reduced levels of YAP in the nuclei of cancer cells. Conclusion This is the first in vivo screening, precisely designed to identify proteins able to interfere with cancer cell invasiveness. EMID2 was selected as the most potent protein, in line with the emerging relevance of the tumor extracellular matrix in controlling cancer cell invasiveness and dissemination, which kills most of cancer patients.
  • Access State: Open Access