Wnt Signaling in the Development of Bone Metastasis

Abstract

Wnt signaling occurs through evolutionarily conserved pathways that affect cellular proliferation and fate decisions during development and tissue maintenance. Alterations in these highly regulated pathways, however, play pivotal roles in various malignancies, promoting cancer initiation, growth and metastasis and the development of drug resistance. The ability of cancer cells to metastasize is the primary cause of cancer mortality. Bone is one of the most frequent sites of metastases that generally arise from breast, prostate, lung, melanoma or kidney cancer. Upon their arrival to the bone, cancer cells can enter a long-term dormancy period, from which they can be reactivated, but can rarely be cured. The activation of Wnt signaling during the bone metastasis process was found to enhance proliferation, induce the epithelial-to-mesenchymal transition, promote the modulation of the extracellular matrix, enhance angiogenesis and immune tolerance and metastasize and thrive in the bone. Due to the complexity of Wnt pathways and of the landscape of this mineralized tissue, Wnt function during metastatic progression within bone is not yet fully understood. Therefore, we believe that a better understanding of these pathways and their roles in the development of bone metastasis could improve our understanding of the disease and may constitute fertile ground for potential therapeutics.