Work

CB2 cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway

Year: 2016

Type: article

Abstract: // Esther Martínez-Martínez 1 , Asunción Martín-Ruiz 1 , Paloma Martín 2 , Virginia Calvo 1 , Mariano Provencio 1 , José M. García 1 1 Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, E-28222 Madrid, Spain 2 Department of Pathology, Hospital Universitario Puerta de Hierro-Majadahonda, E-28222 Madrid, Spain Correspondence to: José M. García, email: [email protected] Keywords: CB 2 , colon cancer, AKT/PKB, JWH-133, proliferation Received: January 11, 2016 Accepted: September 02, 2016 Published: September 12, 2016 ABSTRACT 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.11968

Authors: Esther Martínez-Martínez, Asunción Martín-Ruiz, Paloma Martín, Virginia Calvo, Mariano Provencio, José M. García

Institution: Hospital Universitario Puerta de Hierro Majadahonda

Language: English

Topic: Cannabis and Cannabinoid Research

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Universidad Autónoma de Madrid, Instituto de Salud Carlos III