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CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway

The pharmacological activation of the cannabinoid receptor type 2, CB(2), has been shown to elicit anti-tumoral mechanisms in different cancer types. However, little is known about its endogenous role in tumor pathophysiology, and different studies have attributed pro-tumorigenic properties to this...

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Autores principales: Martínez-Martínez, Esther, Martín-Ruiz, Asunción, Martín, Paloma, Calvo, Virginia, Provencio, Mariano, García, José M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356589/
https://www.ncbi.nlm.nih.gov/pubmed/27634891
http://dx.doi.org/10.18632/oncotarget.11968
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author Martínez-Martínez, Esther
Martín-Ruiz, Asunción
Martín, Paloma
Calvo, Virginia
Provencio, Mariano
García, José M.
author_facet Martínez-Martínez, Esther
Martín-Ruiz, Asunción
Martín, Paloma
Calvo, Virginia
Provencio, Mariano
García, José M.
author_sort Martínez-Martínez, Esther
collection PubMed
description The pharmacological activation of the cannabinoid receptor type 2, CB(2), has been shown to elicit anti-tumoral mechanisms in different cancer types. However, little is known about its endogenous role in tumor pathophysiology, and different studies have attributed pro-tumorigenic properties to this receptor. In a previous work, we showed that CB(2) expression is a poor prognostic factor in colon cancer patients. Here we report that activation of CB(2) with low doses of specific agonists induce cell proliferation and favor the acquisition of aggressive molecular features in colon cancer cells. We show that sub-micromolar concentrations of CB(2)-specific agonists, JWH-133 and HU-308, promote an increase in cell proliferation rate through the activation of AKT/PKB pathway in colon cancer in vitro and in vivo. AKT activation promotes GSK3β inhibition and thus, a more aggressive cell phenotype with the subsequent elevation of SNAIL levels, E-cadherin degradation and β-catenin delocalization from cell membrane. Taken together, our data show that CB(2) activation with sub-micromolar doses of agonists, which could be more similar to endogenous levels of cannabinoids, promote colon cancer progression, implicating that CB(2) could have a pro-tumorigenic endogenous role in colon cancer.
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spelling pubmed-53565892017-03-24 CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway Martínez-Martínez, Esther Martín-Ruiz, Asunción Martín, Paloma Calvo, Virginia Provencio, Mariano García, José M. Oncotarget Research Paper The pharmacological activation of the cannabinoid receptor type 2, CB(2), has been shown to elicit anti-tumoral mechanisms in different cancer types. However, little is known about its endogenous role in tumor pathophysiology, and different studies have attributed pro-tumorigenic properties to this receptor. In a previous work, we showed that CB(2) expression is a poor prognostic factor in colon cancer patients. Here we report that activation of CB(2) with low doses of specific agonists induce cell proliferation and favor the acquisition of aggressive molecular features in colon cancer cells. We show that sub-micromolar concentrations of CB(2)-specific agonists, JWH-133 and HU-308, promote an increase in cell proliferation rate through the activation of AKT/PKB pathway in colon cancer in vitro and in vivo. AKT activation promotes GSK3β inhibition and thus, a more aggressive cell phenotype with the subsequent elevation of SNAIL levels, E-cadherin degradation and β-catenin delocalization from cell membrane. Taken together, our data show that CB(2) activation with sub-micromolar doses of agonists, which could be more similar to endogenous levels of cannabinoids, promote colon cancer progression, implicating that CB(2) could have a pro-tumorigenic endogenous role in colon cancer. Impact Journals LLC 2016-09-12 /pmc/articles/PMC5356589/ /pubmed/27634891 http://dx.doi.org/10.18632/oncotarget.11968 Text en Copyright: © 2016 Martínez-Martínez et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Martínez-Martínez, Esther
Martín-Ruiz, Asunción
Martín, Paloma
Calvo, Virginia
Provencio, Mariano
García, José M.
CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway
title CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway
title_full CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway
title_fullStr CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway
title_full_unstemmed CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway
title_short CB(2) cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway
title_sort cb(2) cannabinoid receptor activation promotes colon cancer progression via akt/gsk3β signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356589/
https://www.ncbi.nlm.nih.gov/pubmed/27634891
http://dx.doi.org/10.18632/oncotarget.11968
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