Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma - Université Grenoble Alpes Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2021

Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma

Fabio Raineri
  • Fonction : Auteur
Mélissande Cossutta
Damien Habert
  • Fonction : Auteur
Matteo Ponzo
Claire Houppe
  • Fonction : Auteur
Benoît Vallée
  • Fonction : Auteur
Michele Boniotto
  • Fonction : Auteur
Mounira Chalabi-Dchar
  • Fonction : Auteur
Philippe Bouvet
Anne Couvelard
  • Fonction : Auteur
Jerome Cros
Anais Debesset
  • Fonction : Auteur
José Cohen
José Courty
  • Fonction : Auteur
Ilaria Cascone

Résumé

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and resistant cancer with no available effective therapy. We have previously demonstrated that nucleolin targeting by N6L impairs tumor growth and normalizes tumor vessels in PDAC mouse models. Here, we investigated new pathways that are regulated by nucleolin in PDAC. We found that N6L and nucleolin interact with β-catenin. We found that the Wnt/β-catenin pathway is activated in PDAC and is necessary for tumor-derived 3D growth. N6L and nucleolin loss of function induced by siRNA inhibited Wnt pathway activation by preventing β-catenin stabilization in PDAC cells. N6L also inhibited the growth and the activation of the Wnt/β-catenin pathway in vivo in mice and in 3D cultures derived from MIA PaCa2 tumors. On the other hand, nucleolin overexpression increased β-catenin stabilization. In conclusion, in this study, we identified β-catenin as a new nucleolin interactor and suggest that the Wnt/β-catenin pathway could be a new target of the nucleolin antagonist N6L in PDAC.

Dates et versions

hal-04551017 , version 1 (18-04-2024)

Identifiants

Citer

Fabio Raineri, Sandrine Bourgoin-Voillard, Mélissande Cossutta, Damien Habert, Matteo Ponzo, et al.. Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma. Cancers, 2021, 13 (12), pp.2986. ⟨10.3390/cancers13122986⟩. ⟨hal-04551017⟩

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