Loss of Cannabinoid Receptor 1 Accelerates Intestinal Tumor Growth

Wang, Dingzhi; Wang, Haibin; Wei, Ning; Backlund, Michael G.; Dey, Sudhansu K.; DuBois, Raymond N.

doi:10.1158/0008-5472.can-08-0896

Cited by 148 publications

(161 citation statements)

References 40 publications

Supporting

Mentioning

151

Contrasting

Order By: Relevance

“…In thyroid, breast, glioma, and prostate cancer cells, Cnr1 agonists inhibited proliferation which could be abrogated by antagonists (18,(41)(42)(43). Moreover, conflicting results have been obtained in colorectal cancer where Cnr1 agonists can induce apoptosis and inhibit growth, whereas antagonist treatment can either accelerate or prevent precancerous lesion formation, depending on the animal model used (37,44,45). However, we could find no contribution of Cnr1 to PAX3-FOXO1-induced myoblast growth.…”

Section: Discussioncontrasting

confidence: 67%

“…This increased invasive and metastatic capacity contribute to the poorer prognosis associated with ARMS (1-3). Because Cnr1 has been associated with cell migration and tumor invasiveness (19,20,(37)(38)(39), we wished to determine whether Cnr1 played a role in this PAX3-FOXO1-dependent phenotype.…”

Section: Cnr1 Upregulation Does Not Contribute To Proliferation Diffmentioning

confidence: 99%

See 1 more Smart Citation

PAX3-FOXO1 Induces Cannabinoid Receptor 1 to Enhance Cell Invasion and Metastasis

2011

View full text Add to dashboard Cite

Alveolar rhabdomyosarcoma (ARMS) is a muscle-derived childhood tumor characterized by production of oncogenic PAX3/7-FOXO1 chimeric transcription factors. While downstream targets of the PAX3-FOXO1 oncoprotein in ARMS have been defined, the functional relevance of these targets is unclear. Here, we show that upregulation of the cannabinoid receptor 1 (Cnr1/Cb1) by PAX3-FOXO1 in mouse primary myoblasts and ARMS cell lines, contributes to PAX3-FOXO1 phenotypes, both in vivo and in vitro. In primary myoblasts, Cnr1 was dispensable for PAX3-FOXO1 to mediate cell proliferation, differentiation, or transformation; however, Cnr1 function was essential to increase the invasive capacity conferred by PAX3-FOXO1 overexpression in these cells. Genetic or pharmacologic abrogation of Cnr1 inhibited the enhanced basement membrane invasion induced by PAX3-FOXO1. Cnr1 loss by either route also dramatically reduced lung metastasis formation. Taken together, our findings strongly implicate Cnr1 as a novel tractable target to inhibit ARMS invasion and metastasis. Cancer Res; 71(24); 7471-80. Ó2011 AACR.

show abstract

Section: Discussioncontrasting

confidence: 67%

Section: Cnr1 Upregulation Does Not Contribute To Proliferation Diffmentioning

confidence: 99%

PAX3-FOXO1 Induces Cannabinoid Receptor 1 to Enhance Cell Invasion and Metastasis

2011

View full text Add to dashboard Cite

show abstract

“…Moreover, several studies confirmed proapoptotic and antiproliferative effects of cannabinoids in different cancer cells by mechanisms involving, for instance, de novo synthesis of ceramide (Galve-Roperh et al, 2000;Hinz et al, 2004) or activation of mitogen-activated protein kinases (GalveRoperh et al, 2000;Herrera et al, 2005). Furthermore, recent data support the hypothesis that cannabinoid receptors together with endogenously produced agonists contribute to an endogenous defense mechanism against tumorigenesis Ligresti et al, 2003;Di Marzo et al, 2004;Kishimoto et al, 2005;Wang et al, 2008).…”

mentioning

confidence: 87%

Antitumorigenic Effects of Cannabinoids beyond Apoptosis

Freimuth¹,

Ramer²,

Hinz³

2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

According to the World Health Organization, the cases of death caused by cancer will have been doubled until the year 2030. By 2010, cancer is expected to be the number one cause of death. Therefore, it is necessary to explore novel approaches for the treatment of cancer. Over past years, the antitumorigenic effects of cannabinoids have emerged as an exciting field in cancer research. Apart from their proapoptotic and antiproliferative action, recent research has shown that cannabinoids may likewise affect tumor cell angiogenesis, migration, invasion, adhesion, and metastasization. This review will summarize the data concerning the influence of cannabinoids on these locomotive processes beyond modulation of cancer cell apoptosis and proliferation. The findings discussed here provide a new perspective on the antitumorigenic potential of cannabinoids.

show abstract

“…We have recently shown that activation of the CB1 receptor by the plant-derived cannabinoid, Δ 9 -tetrahydrocannabinol (THC) induces CB1-dependent apoptosis via inhibition of both RAS-MAPK/ERK and PI3K-AKT signalling cascades in colon cancer cells, (two key survival pathways frequently deregulated in colorectal cancer (13). Furthermore, activation of CB1 was recently reported to attenuate intestinal tumour growth in Apc(Min/ + ) mice suggesting that the endogenous cannabinoid system may represent a potential therapeutic target for prevention or treatment of colorectal cancer (14).…”

Section: Introductionmentioning

confidence: 99%

The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells

Paraskeva¹

2010

Int J Oncol

View full text Add to dashboard Cite

Abstract. Despite recent advances in understanding colorectal tumour biology, there is still a need to improve the 5-year survival rate of patients with colorectal cancer as approximately 40% of patients presenting with advanced disease will remain resistant to therapy. One of the major contributing factors in resistance to therapy is the failure of colorectal tumour cells to undergo apoptosis. Hence there is an urgent need to develop novel therapeutic approaches that can target apoptosis-resistant cells. To this end, we investigated the potential efficacy of the endogenous cannabinoid anandamide to induce cell death in apoptosis-resistant colon cancer cells. Here, for the first time, we show that anandamide can induce cell death in the apoptosis-resistant HCT116 Bax -/-colorectal cell line. Importantly, we provide direct genetic evidence that this induction of cell death is dependent on COX-2 expression. Interestingly, increased COX-2 expression also sensitised the SW480 colorectal cancer cell line (low endogenous COX-2) to anandamide-induced death, whereas COX-2 suppression by RNAi inhibited anandamide-induced cell death in the HCA7 colorectal cancer cell line (high endogenous COX-2 expression). This COX-2-dependent death was independent of cannabinoid receptor engagement (CB1 or CB2), and not a direct consequence of reactive oxygen species (ROS) formation. This study demonstrates a novel utilisation for COX-2 expression, targeting apoptotic defective colorectal cancer cells for destruction by anandamide. As COX-2 is not expressed in the normal colorectal epithelium, but highly expressed in colorectal tumours and apoptosis resistance contributes to treatment failure, these data suggest that anandamide has the potential to be an effective therapeutic in colorectal cancer.

show abstract

Loss of Cannabinoid Receptor 1 Accelerates Intestinal Tumor Growth

Cited by 148 publications

References 40 publications

PAX3-FOXO1 Induces Cannabinoid Receptor 1 to Enhance Cell Invasion and Metastasis

PAX3-FOXO1 Induces Cannabinoid Receptor 1 to Enhance Cell Invasion and Metastasis

Antitumorigenic Effects of Cannabinoids beyond Apoptosis

The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells

Contact Info

Product

Resources

About