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

Amy D Marshall1, Irina Lagutina, Gerard C Grosveld

  • 1Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Cancer Research
|November 1, 2011
PubMed

Insights

Childhood alveolar rhabdomyosarcoma (ARMS) invasion is driven by cannabinoid receptor 1 (Cnr1). Inhibiting Cnr1 blocks ARMS cell invasion and metastasis, offering a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Alveolar rhabdomyosarcoma (ARMS) is a pediatric muscle tumor driven by PAX3/7-FOXO1 fusion proteins.
  • Downstream targets of PAX3-FOXO1 are known, but their functional roles in ARMS progression remain unclear.

Purpose of the Study:

  • To investigate the role of cannabinoid receptor 1 (Cnr1) in mediating PAX3-FOXO1-driven phenotypes in ARMS.
  • To determine if Cnr1 is a potential therapeutic target for inhibiting ARMS invasion and metastasis.

Main Methods:

  • Utilized mouse primary myoblasts and ARMS cell lines.
  • Assessed the impact of PAX3-FOXO1 overexpression on Cnr1 levels.
  • Investigated the effects of genetic or pharmacologic Cnr1 inhibition on cell invasion and metastasis in vitro and in vivo.

Main Results:

  • PAX3-FOXO1 upregulates Cnr1 expression in myoblasts and ARMS cells.
  • Cnr1 is essential for PAX3-FOXO1-induced cell invasion and basement membrane penetration.
  • Blocking Cnr1 function significantly reduces lung metastasis formation in vivo.

Conclusions:

  • Cannabinoid receptor 1 (Cnr1) is a key mediator of ARMS invasion and metastasis.
  • Targeting Cnr1 represents a novel therapeutic strategy to inhibit ARMS progression.

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