Loss of the vitamin D receptor in human breast cancer cells promotes epithelial to mesenchymal cell transition and skeletal colonisation
Expression of the vitamin D receptor (VDR) is thought to be associated with neoplastic progression. However, the role of the VDR in breast cancer metastasis to bone, and the molecular mechanisms underlying this process are unknown. Employing a rodent model (female Balb/c nu/nu mice) of systemic metastasis, we here demonstrate that knock-down of the VDR strongly increases the metastatic potential of MDA-MB-231 human breast cancer cells to bone, resulting in significantly greater skeletal tumour burden. Ablation of VDR expression promotes cancer cell mobility (migration) and invasiveness, thereby facilitating skeletal colonisation. Mechanistically, these changes in tumour cell behaviour are attributable to shifts in the expression of proteins involved in cell adhesion, proliferation and cytoskeletal organisation, patterns characteristic for epithelial to mesenchymal cell transition (EMT). In keeping with these experimental findings, analyses of human breast cancer specimens corroborated the association between VDR expression, EMT-typical changes in protein expression patterns, and clinical prognosis. Loss of the VDR in human breast cancer cells marks a critical point in oncogenesis by inducing epithelial-to-mesenchymal cell transition, promoting the dissemination of cancer cells and facilitating the formation of tumour colonies in bone. This article is protected by copyright. All rights reserved.
|ISBN||1523-4681 (Electronic) 0884-0431 (Linking)|
|Authors||Horas, K.; Zheng, Y.; Fong-Yee, C.; Macfarlane, E.; Manibo, J.; Chen, Y.; Qiao, J.; Gao, M.; Haydar, N.; McDonald, M. M.; Croucher, P. I.; Zhou, H.; Seibel, M. J.|
|Responsible Garvan Author||Dr Michelle McDonald|
|Publisher Name||JOURNAL OF BONE AND MINERAL RESEARCH|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/30995345|