Journal article

Pharmacologic inhibition of vacuolar H plus ATPase reduces physiologic and oncogenic Notch signaling

Francis Kobia, Serena Duchi, Gianluca Deflorian, Thomas Vaccari

MOLECULAR ONCOLOGY | WILEY | Published : 2014

Abstract

Notch signaling in prominently involved in growth regulation in metazoan tissues. Because of this, Notch is often upregulated in cancer and current efforts point to developing drugs that block its activation. Notch receptor endocytosis towards acidic compartments is a recently appreciated determinant of signaling activation. Vacuolar H(+) ATPase (V-ATPase) is responsible for acidification of endocytic organelles and mutants in V-ATPase subunit encoding genes in model organisms have been recently shown to display loss of Notch signaling. Here, we show that administration of BafilomycinA1 (BafA1), a highly specific V-ATPase inhibitor decreases Notch signaling during Drosophila and Zebrafish de..

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Grants

Awarded by Telethon Italia


Awarded by Associazione Italiana Ricerca sul Cancro


Funding Acknowledgements

We thank Fen-Biao Gao, Jim Posakony, David Bilder, Iswar Hariharan, Urban Lendhal and Pier Paolo Di Fiore for reagents. We also thank Nina Offenhauser, Marisa Oppizzi and Salvatore Pece for critically reading the manuscript. F.K. was supported in part by IIT@SEMM and S.D. was supported by a fellowship from Associazione Italiana Ricerca contro il Cancro. Research in the lab of T.V. is funded by a new unit start-up grant from Associazione Italiana Ricerca contro il Cancro and by Telethon Italia. Work in the lab of T.V. is supported by grant# 6118 from Associazione Italiana Ricerca sul Cancro, and by grant# GGP13225 from Telethon Italia.