Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles Cancers Year : 2021

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

Fabio Raineri
  • Function : Author
  • PersonId : 1102241
Damien Habert
  • Function : Author
  • PersonId : 1102243
Claire Houppe
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  • PersonId : 1102244
Benoît Vallée
  • Function : Author
  • PersonId : 1102245
Anais Debesset
  • Function : Author
  • PersonId : 1102246
José L Cohen
José Courty

Abstract

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.
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hal-03262175 , version 1 (16-06-2021)

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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-03262175⟩
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