The precise molecular mechanisms that coordinate apoptosis and autophagy in cancer remain to be determined. Here, we provide evidence that the tumor suppressor promyelocytic leukemia protein (PML) controls autophagosome formation at mitochondria-associated membranes (MAMs) and, thus, autophagy induction. Our in vitro and in vivo results demonstrate how PML functions as a repressor of autophagy. PML loss promotes tumor development, providing a growth advantage to tumor cells that use autophagy as a cell survival strategy during stress conditions. These findings demonstrate that autophagy inhibition could be paired with a chemotherapeutic agent to develop anticancer strategies for tumors that present PML downregulation.

PML at Mitochondria-Associated Membranes Is Critical for the Repression of Autophagy and Cancer Development

MISSIROLI, Sonia
Co-primo
;
BONORA, Massimo
Co-primo
;
PATERGNANI, Simone
Co-primo
;
POLETTI, Federica;PERRONE, Mariasole;GAFA', Roberta;MAGRI, Eros;RAIMONDI, Andrea Francesco;LANZA, Giovanni;PINTON, Paolo
Penultimo
;
GIORGI, Carlotta
Ultimo
2016

Abstract

The precise molecular mechanisms that coordinate apoptosis and autophagy in cancer remain to be determined. Here, we provide evidence that the tumor suppressor promyelocytic leukemia protein (PML) controls autophagosome formation at mitochondria-associated membranes (MAMs) and, thus, autophagy induction. Our in vitro and in vivo results demonstrate how PML functions as a repressor of autophagy. PML loss promotes tumor development, providing a growth advantage to tumor cells that use autophagy as a cell survival strategy during stress conditions. These findings demonstrate that autophagy inhibition could be paired with a chemotherapeutic agent to develop anticancer strategies for tumors that present PML downregulation.
2016
Missiroli, Sonia; Bonora, Massimo; Patergnani, Simone; Poletti, Federica; Perrone, Mariasole; Gafa', Roberta; Magri, Eros; Raimondi, Andrea Francesco; Lanza, Giovanni; Tacchetti, Carlo; Kroemer, Guido; Pandolfi, Pier Paolo; Pinton, Paolo; Giorgi, Carlotta
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2353723
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