The Wnt signaling pathway: implications for therapy in osteosarcoma

Abstract

Osteosarcoma is the most common primary bone malignancy, with a high propensity for local invasion, early metastasis and relapse. While the molecular mechanisms behind osteosarcoma development and metastasis have not yet been fully elucidated, research has highlighted an important role for Wnt signaling. Several Wnt ligands, receptors and coreceptors are highly expressed in osteosarcoma cell lines, while Wnt inhibitors are downregulated. As a result, research has begun to identify mechanisms with which to inhibit Wnt signaling. The use of Wnt pathway inhibitors and the targeting of c-Met, a Wnt regulated proto-oncogene, may be two possible mechanisms for treatment of osteosarcoma. In addition, as the Wnt signaling pathway is a regulator of stem cells, reagents that function as Wnt inhibitors are currently under investigation as inhibitors of cancer stem cell proliferation. Research involving the Wnt signaling pathway and cancer stem cells holds promise for novel treatment options in the future.

Keywords::

• cancer stem cells
• c-Met
• DKK3
• Frzb
• LRP5
• osteosarcoma
• WIF-1
• Wnt signaling

Financial & competing interests disclosure

Bang H Hoang has received grant support from the NIH (grant no. CA116003), the Chao Family Comprehensive Cancer Center, the Aircast Foundation, the American Cancer Society, and the Orthopaedic Research and Education Foundation. Xiaolin Zi is supported by the NIH (grant no. CA129793 and CA122558) and the AICR (grant no. 41493). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.