RT Journal Article
T1 Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization
A1 Hernández Tiedra, Sonia
A1 Fabriàs, Gemma
A1 Dávila, David
A1 Salanueva, Iñigo J.
A1 Casas, Josefina
A1 Montes, L.Ruth
A1 Antón, Zuriñe
A1 GarcíaTaboada, Elena
A1 Salazar Roa, María
A1 Lorente Pérez, Mar
A1 Nylandsted, Jesper
A1 Armstrong, Jane
A1 López Valero, Israel
A1 McKee, Christopher S.
A1 Serrano Puebla, Ana
A1 García López, Roberto
A1 González Martínez, José
A1 Abad, José L.
A1 Kentaro, Hanada
A1 Boya, Patricia
A1 Goñi, Félix
A1 Guzmán, Manuel
A1 Lovat, Penny
A1 Jäättelä, Marja
A1 Alonso, Alicia
A1 Velasco, Guillermo
AB Autophagy is considered primarily a cell survival process, although it can also lead to cell death. However, the factors that dictate the shift between these 2 opposite outcomes remain largely unknown. In this work, we used D9 -tetrahydrocannabinol (THC, the main active component of marijuana, a compound that triggers autophagy-mediated cancer cell death) and nutrient deprivation (an autophagic stimulus that triggers cytoprotective autophagy) to investigate the precise molecular mechanisms responsible for the activation of cytotoxic autophagy in cancer cells. By using a wide array of experimental approaches we show that THC (but not nutrient deprivation) increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum of glioma cells, and this alteration is directed to autophagosomes and autolysosomes to promote lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. These findings pave the way to clarify the regulatory mechanisms that determine the selective activation of autophagy-mediated cancer cell death.
PB Taylor & Francis
SN 1554-8627, ESSN: 1554-8635
YR 2016
FD 2016-09-16
LK https://hdl.handle.net/20.500.14352/18401
UL https://hdl.handle.net/20.500.14352/18401
LA eng
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III (ISCIII) / FEDER
NO Fundación Mutua Madrileña
NO Generalitat de Catalunya
NO Gobierno Vasco
DS Docta Complutense
RD 4 may 2024