Author/Authors :
Carracedo، نويسنده , , Arkaitz and Lorente، نويسنده , , Mar and Egia، نويسنده , , Ainara and Blلzquez، نويسنده , , Cristina and Garcيa، نويسنده , , Stephane and Giroux، نويسنده , , Valentin and Malicet، نويسنده , , Cedric and Villuendas، نويسنده , , Raquel and Gironella، نويسنده , , Meritxell and Gonzلlez-Feria، نويسنده , , Luis and Piris، نويسنده , , Miguel ءngel and Iovanna، نويسنده , , Juan L. and Guzmلn، نويسنده , , Manuel and Velasco، نويسنده , , Guillermo، نويسنده ,
Abstract :
Summary
the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.
