Breast Cancer

Biography

Biography: Pascale A. Cohen

Abstract

Newly discovered molecular functions of ZNF217 indicate that it orchestrates complex intracellular circuits as a new key regulator of tumorigenesis. This talk will focus on recent research on ZNF217 driven molecular functions in human breast cancers, revisiting major hallmarks of cancer and highlighting the downstream molecular targets and signaling pathways of ZNF217. Among the ZNF217 driven mechanisms which lead to aggressiveness and metastasis in breast cancer our group discovered that the ZNF217 oncogene is a crucial mediator and indicator of the bone metastatic process. Indeed, patients possessing high ZNF217  m-RNA expression levels in primary breast tumors had a significantly higher risk of developing bone metastases. ZNF217 stably transfected MDA-MB-231 breast cancer cells (MDA-MB-231-ZNF217) displayed the dysregulated expression of a set of genes with bone homing/bone metastasis characteristics, which clearly overlapped with two previously described osteolytic bone metastasis gene signatures and also newly highlighted the bone morphogenetic protein (BMP) pathway. This latter was activated in MDA-MB-231-ZNF217 cells and its silencing by several inhibitors was sufficient to rescue ZNF217 dependent cell migration, cell invasion or chemotaxis towards the bone environment. Finally, using in vivo non-invasive multimodal imaging, we found that ZNF217 increases the metastatic growth rate in the bone and accelerates the development of severe osteolytic lesions. Altogether, this study highlights that in breast cancer, ZNF217 is a new indicator for the emergence of bone metastasis and that future therapies targeting ZNF217 and/or of the BMP signaling pathway may be beneficial for patients by preventing the development of bone metastasis.