Primary tumor-derived systemic nANGPTL4 inhibits metastasis

Hübers, Corinne and Abdul Pari, Ashik Ahmed and Grieshober, Denise and Petkov, Martin and Schmidt, Alexander and Messmer, Tatjana and Heyer, Christian Moritz and Schölch, Sebastian and Kapel, Stephanie S. and Gengenbacher, Nicolas and Singhal, Mahak and Schieb, Benjamin and Fricke, Claudine and Will, Rainer and Remans, Kim and Utikal, Jochen Sven and Reissfelder, Christoph and Schlesner, Matthias and Hodivala-Dilke, Kairbaan M. and Kersten, Sander and Goerdt, Sergij and Augustin, Hellmut G. and Felcht, Moritz. (2023) Primary tumor-derived systemic nANGPTL4 inhibits metastasis. Journal of Experimental Medicine, 220 (1). pp. 1-18.

[img] PDF - Published Version
Available under License CC BY-NC-SA (Attribution-NonCommercial-ShareAlike).


Official URL: https://edoc.unibas.ch/90863/

Downloads: Statistics Overview


Primary tumors and distant site metastases form a bidirectionally communicating system. Yet, the molecular mechanisms of this crosstalk are poorly understood. Here, we identified the proteolytically cleaved fragments of angiopoietin-like 4 (ANGPTL4) as contextually active protumorigenic and antitumorigenic contributors in this communication ecosystem. Preclinical studies in multiple tumor models revealed that the C-terminal fragment (cANGPTL4) promoted tumor growth and metastasis. In contrast, the N-terminal fragment of ANGPTL4 (nANGPTL4) inhibited metastasis and enhanced overall survival in a postsurgical metastasis model by inhibiting WNT signaling and reducing vascularity at the metastatic site. Tracing ANGPTL4 and its fragments in tumor patients detected full-length ANGPTL4 primarily in tumor tissues, whereas nANGPTL4 predominated in systemic circulation and correlated inversely with disease progression. The study highlights the spatial context of the proteolytic cleavage-dependent pro- and antitumorigenic functions of ANGPTL4 and identifies and validates nANGPTL4 as a novel biomarker of tumor progression and antimetastatic therapeutic agent.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
edoc DOI:
Last Modified:06 Dec 2022 10:04
Deposited On:06 Dec 2022 10:04

Repository Staff Only: item control page