Title

Role of the WWOX tumor suppressor gene in bone homeostasis and the pathogenesis of osteosarcoma

UMMS Affiliation

Department of Cell Biology

Date

4-3-2011

Document Type

Article

Medical Subject Headings

Oxidoreductases; Tumor Suppressor Proteins

Disciplines

Cell Biology

Abstract

Osteosarcoma is the most common primary bone malignancy in children with unknown etiology and often with poor clinical outcome. In recent years, a critical role has emerged for the WW domain-containing oxidoreductase (WWOX) in osteosarcoma and bone biology. WWOX is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma and a bone metabolic disease characterized by hypocalcemia and osteopenia. Studies of human osteosarcomas have revealed that the WWOX gene is deleted in 30% of cases and WWOX protein is absent or reduced in approximately 60% of tumors. Further, WWOX levels are attenuated in the majority of osteosarcoma cells, in which ectopic expression is associated with reduced proliferation, migration, invasion and tumorigenicity. At the molecular level, WWOX associates with RUNX2 and suppresses its transcriptional activity in osteoblasts and in cancer cells. This review provides new insights on the current knowledge of the spectrum of WWOX activities and future directions for the role of WWOX in bone biology and osteosarcoma.

Rights and Permissions

Citation: Am J Cancer Res. 2011;1(5):585-94. Epub 2011 Apr 3.

Related Resources

Link to Article in PubMed