The Wnt inhibitor dickkopf-1: a link between breast cancer and bone metastases

Breast cancer is the second leading cause of cancer death in women and metastasizes to bone in greater than 80 % of advanced-disease patients. Once breast cancer bone metastases are established, the disease is incurable and drives numerous complications that increase morbidity and diminish patients' quality of life. Many mechanisms have been implicated in bone metastases of breast cancer. The critical role of Wnt signalling pathway inhibition in initiating bone lesions has been demonstrated in a variety of bone diseases and tumours. Overexpression of dickkopf-1 (Dkk1) protein, a negative regulator of the Wnt/beta-catenin pathway, has been found in breast cancer cell lines that form osteolytic metastases preferentially and in serum from breast cancer patients with osteolytic bone metastases. Further understanding of the mechanistic role of Dkk1 as a link between primary breast tumours and secondary osteolytic bone metastases may facilitate development of anti-Dkk1 antibody therapeutic tools.