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Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells

Trouvilliez, Sarah; Cicero, Julien; Lévêque, Romain; Aubert, Léo; Corbet, Cyril; Van Outryve, Alexandre; Streule, Karolin 1,2; Angrand, Pierre-Olivier; Völkel, Pamela; Magnez, Romain; Brysbaert, Guillaume; Mysiorek, Caroline; Gosselet, Fabien; Bourette, Roland; Adriaenssens, Eric; Thuru, Xavier; Lagadec, Chann; de Ruyck, Jérôme; Orian-Rousseau, Véronique 1; ... mehr

Abstract:

Background

CD44 is a multifunctional membrane glycoprotein. Through its heparan sulfate chain, CD44 presents growth factors to their receptors. We have shown that CD44 and Tropomyosin kinase A (TrkA) form a complex following nerve growth factor (NGF) induction. Our study aimed to understand how CD44 and TrkA interact and the consequences of inhibiting this interaction regarding the pro-tumoral effect of NGF in breast cancer.
Methods

After determining which CD44 isoforms (variants) are involved in forming the TrkA/CD44 complex using proximity ligation assays, we investigated the molecular determinants of this interaction. By molecular modeling, we isolated the amino acids involved and confirmed their involvement using mutations. A CD44v3 mimetic peptide was then synthesized to block the TrkA/CD44v3 interaction. The effects of this peptide on the growth, migration and invasion of xenografted triple-negative breast cancer cells were assessed. Finally, we investigated the correlations between the expression of the TrkA/CD44v3 complex in tumors and histo-pronostic parameters.
Results

We demonstrated that isoform v3 (CD44v3), but not v6, binds to TrkA in response to NGF stimulation. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000144728
Veröffentlicht am 14.04.2022
Originalveröffentlichung
DOI: 10.1186/s13046-022-02314-4
Scopus
Zitationen: 8
Web of Science
Zitationen: 6
Dimensions
Zitationen: 9
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 12.2022
Sprache Englisch
Identifikator ISSN: 1756-9966
KITopen-ID: 1000144728
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in Journal of Experimental & Clinical Cancer Research
Verlag Springer Fachmedien Wiesbaden
Band 41
Heft 1
Seiten Art.-Nr. 110
Vorab online veröffentlicht am 28.03.2022
Nachgewiesen in Dimensions
Scopus
Web of Science
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