The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone

Aurélie Bellanger, Caterina F. Donini, Julie A. Vendrell, Jonathan Lavaud, Irma Machuca-Gayet, Maëva Ruel, Julien Vollaire, Evelyne Grisard, B. Györffy, Ivan Bièche, Olivier Peyruchaud, Jean Luc Coll, Isabelle Treilleux, Véronique Maguer-Satta, Véronique Josserand, Pascale A. Cohen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Bone metastasis affects >70% of patients with advanced breast cancer. However, the molecular mechanisms underlying this process remain unclear. On the basis of analysis of clinical datasets, and in vitro and in vivo experiments, we report that the ZNF217 oncogene is a crucial mediator and indicator of bone metastasis. Patients with high ZNF217 mRNA expression levels in primary breast tumours had a higher risk of developing bone metastases. MDA-MB-231 breast cancer cells stably transfected with ZNF217 (MDA-MB-231-ZNF217) showed the dysregulated expression of a set of genes with bone-homing and metastasis characteristics, which overlapped with two previously described ‘osteolytic bone metastasis’ gene signatures, while also highlighting the bone morphogenetic protein (BMP) pathway. The latter was activated in MDA-MB-231-ZNF217 cells, and its silencing by inhibitors (Noggin and LDN-193189) was sufficient to rescue ZNF217-dependent cell migration, invasion or chemotaxis towards the bone environment. Finally, by using non-invasive multimodal in vivo imaging, we found that ZNF217 increases the metastatic growth rate in the bone and accelerates the development of severe osteolytic lesions. Altogether, the findings of this study highlight ZNF217 as an indicator of the emergence of breast cancer bone metastasis; future therapies targeting ZNF217 and/or the BMP signalling pathway may be beneficial by preventing the development of bone metastases.

Original languageEnglish
Pages (from-to)73-89
Number of pages17
JournalJournal of Pathology
Volume242
Issue number1
DOIs
Publication statusPublished - May 1 2017

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Keywords

  • BMP pathway
  • bone metastasis
  • breast cancer
  • oncogene
  • ZNF217

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Bellanger, A., Donini, C. F., Vendrell, J. A., Lavaud, J., Machuca-Gayet, I., Ruel, M., Vollaire, J., Grisard, E., Györffy, B., Bièche, I., Peyruchaud, O., Coll, J. L., Treilleux, I., Maguer-Satta, V., Josserand, V., & Cohen, P. A. (2017). The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone. Journal of Pathology, 242(1), 73-89. https://doi.org/10.1002/path.4882