The canonical Wnt-beta-catenin pathway in development and chemotherapy of osteosarcoma

Abstract

The canonical Wnt-beta -catenin signaling pathway is a key component of normal skeletal development and disease. Alterations within this signaling pathway have been described in human and canine osteosarcoma (OS); however, debate exists as to whether or not alterations in this pathway contribute to OS development in humans. In metastatic OS, the Wnt-β- catenin pathway promotes the invasion and migration of OS cells and β-catenin acts as a biological marker of OS with the potential to metastasize to the lung. The participation of the Wnt-β-catenin pathway in OS development and metastasis is regulated by several factors, including hormones and alkaline phosphatase (ALP). This pathway is also involved in the resistance of OS to chemotherapy, especially in resistance to all three drugs used in standard chemotherapy, i.e. doxorubicin, cisplatin and methotrexate (MTX). In this review, we will summarize recent findings regarding the Wnt-β-catenin pathway in OS development and chemotherapy.