Universidad Complutense de Madrid
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Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization

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Hernández Tiedra, Sonia y Fabriàs, Gemma y Dávila, David y Salanueva, Iñigo J. y Casas, Josefina y Montes, L.Ruth y Antón, Zuriñe y GarcíaTaboada, Elena y Salazar Roa, María y Lorente Pérez, Mar y Nylandsted, Jesper y Armstrong, Jane y López Valero, Israel y McKee, Christopher S. y Serrano Puebla, Ana y García López, Roberto y González Martínez, José y Abad, José L. y Kentaro, Hanada y Boya, Patricia y Goñi, Félix y Guzmán, Manuel y Lovat, Penny y Jäättelä, Marja y Alonso, Alicia y Velasco, Guillermo (2016) Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization. Autophagy, 12 (11). pp. 2213-2229. ISSN 1554-8627, ESSN: 1554-8635

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URL Oficial: https://doi.org/10.1080/15548627.2016.1213927



Resumen

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.


Tipo de documento:Artículo
Palabras clave:Autophagy; cancer; cannabinoids; cell death; sphingolipids
Materias:Ciencias Biomédicas > Biología > Biología molecular
Ciencias Biomédicas > Biología > Bioquímica
Código ID:46554
Depositado:23 Feb 2018 09:16
Última Modificación:23 Feb 2018 09:16

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