Document Detail


PAX3-FOXO1 induces cannabinoid receptor 1 to enhance cell invasion and metastasis.
MedLine Citation:
PMID:  22037868     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 up-regulation 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 over-expression in these cells. Genetic or pharmacological 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.
Authors:
Amy D Marshall; Irina Lagutina; Gerard C Grosveld
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-28
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Dept of Genetics, St Jude Children's Research Hosp.
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