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

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

Content Provider	MDPI
Author	Beno, ît Vallée Raineri, Fabio Bourgoin-Voillard, Sandrine Cossutta, Mélissande Habert, Damien Ponzo, Matteo Houppe, Claire Boniotto, Michele Chalabi-Dchar, Mounira Bouvet, Philippe Couvelard, Anne Cros, Jerome Debesset, Anais Cohen, José Courty, José Cascone, Ilaria
Copyright Year	2021
Description	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.
Starting Page	2986
e-ISSN	20726694
DOI	10.3390/cancers13122986
Journal	Cancers
Issue Number	12
Volume Number	13
Language	English
Publisher	MDPI
Publisher Date	2021-06-15
Access Restriction	Open
Subject Keyword	Cancers Pathology Pancreatic Ductal Adenocarcinoma Nucleolin N6l Wnt/β-catenin Pathway Tumor Microenvironment Cancer Therapy
Content Type	Text
Resource Type	Article

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