Canna~Fangled Abstracts

PAX3-FOXO1 induces cannabinoid receptor 1 to enhance cell invasion and metastasis.

By December 15, 2011 No Comments
 2011 Dec 15;71(24):7471-80. doi: 10.1158/0008-5472.CAN-11-0924. Epub 2011 Oct 28.

pm1PAX3-FOXO1 induces cannabinoid receptor 1 to enhance cell invasion and metastasis.

Abstract

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.
PMID:

 22037868
[PubMed – indexed for MEDLINE] Publication Types, MeSH Terms, Substances

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