The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells.
One of 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.
Carracedo
Arkaitz
A
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain.
Lorente
Mar
M
Egia
Ainara
A
Blázquez
Cristina
C
García
Stephane
S
Giroux
Valentin
V
Malicet
Cedric
C
Villuendas
Raquel
R
Gironella
Meritxell
M
González-Feria
Luis
L
Piris
Miguel Angel
MA
Iovanna
Juan L
JL
Guzmán
Manuel
M
Velasco
Guillermo
G
D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D002186:Cannabinoids / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D051701:Activating Transcription Factor 4; D051792:Basic Helix-Loop-Helix Proteins; D002186:Cannabinoids; D018797:Cell Cycle Proteins; D013759:Dronabinol; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; D051742:Transcription Factor CHOP; C497109:ATF4 protein, human; C497249:DDIT3 protein, human; C491643:NUPR1 protein, human; C474831:TRIB3 protein, human