title: Molecular alterations that drive breast cancer metastasis to bone.
abstract: Epithelial cancers including breast and prostate commonly progress to form incurable bone metastases. For this to occur, cancer cells must adapt their phenotype and behaviour to enable detachment from the primary tumour, invasion into the vasculature, and homing to and subsequent colonisation of bone. It is widely accepted that the metastatic process is driven by the transformation of cancer cells from a sessile epithelial to a motile mesenchymal phenotype through epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into the circulation provides the conduit for cells to metastasise to distant organs. However, accumulating evidence suggests that EMT is not sufficient for metastasis to occur and that specific tissue-homing factors are required for tumour cells to lodge and grow in bone. Once tumour cells are disseminated in the bone environment, they can revert into an epithelial phenotype through the reverse process of mesenchymal-epithelial transition (MET) and form secondary tumours. In this review, we describe the molecular alterations undertaken by breast cancer cells at each stage of the metastatic cascade and discuss how these changes facilitate bone metastasis.
authors.affiliation: Academic Unit of Clinical Oncology, Department of Oncology, Medical School, University of Sheffield , Sheffield, UK.
authors.forename: Penelope D
authors.initials: PD
authors.lastname: Ottewell
authors.affiliation: Academic Unit of Clinical Oncology, Department of Oncology, Medical School, University of Sheffield , Sheffield, UK.
authors.forename: Liam
authors.initials: L
authors.lastname: O'Donnell
authors.affiliation: Academic Unit of Clinical Oncology, Department of Oncology, Medical School, University of Sheffield , Sheffield, UK.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Holen
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