Article (Scientific journals)
Loss of Ambra1 promotes melanoma growth and invasion.
Di Leo, Luca; Bodemeyer, Valérie; Bosisio, Francesca M. et al.
2021In Nature Communications, 12 (1), p. 2550
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Abstract :
[en] Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Di Leo, Luca
Bodemeyer, Valérie
Bosisio, Francesca M.
Claps, Giuseppina
Carretta, Marco
Rizza, Salvatore
Faienza, Fiorella
Frias, Alex
Khan, Shawez
Bordi, Matteo
PIRES PACHECO, Maria Irene ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Di Martino, Julie
Bravo-Cordero, Jose J.
Daniel, Colin J.
Sears, Rosalie C.
Donia, Marco
Madsen, Daniel H.
Guldberg, Per
Filomeni, Giuseppe
SAUTER, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Robert, Caroline
De Zio, Daniela
Cecconi, Francesco
More authors (13 more) Less
External co-authors :
yes
Language :
English
Title :
Loss of Ambra1 promotes melanoma growth and invasion.
Publication date :
2021
Journal title :
Nature Communications
ISSN :
2041-1723
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
12
Issue :
1
Pages :
2550
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 11 May 2021

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