| First Author | Marshall AD | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 24 | Pages | 7471-80 |
| PubMed ID | 22037868 | Mgi Jnum | J:178844 |
| Mgi Id | MGI:5300410 | Doi | 10.1158/0008-5472.CAN-11-0924 |
| Citation | Marshall AD, et al. (2011) PAX3-FOXO1 Induces Cannabinoid Receptor 1 to Enhance Cell Invasion and Metastasis. Cancer Res 71(24):7471-80 |
| abstractText | 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. (c)2011 AACR. |
