Early-stage metastasis requires Mdm2 and not p53 gain of function

Paula M. Hauck, Eric R. Wolf, David J. Olivos, Christopher N. Batuello, Kyle C. McElyea, Ciaran P. McAtarsney, R. Michael Cournoyer, George E. Sandusky, Lindsey D. Mayo

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Metastasis of cancer cells to distant organ systems is a complex process that is initiated with the programming of cells in the primary tumor. The formation of distant metastatic foci is correlated with poor prognosis and limited effective treatment options. We and others have correlated Mouse double minute 2 (Mdm2) with metastasis; however, the mechanisms involved have not been elucidated. Here, it is reported that shRNA-mediated silencing of Mdm2 inhibits epithelial–mes-enchymal transition (EMT) and cell migration. In vivo analysis demonstrates that silencing Mdm2 in both post-EMT and basal/triple-negative breast cancers resulted in decreased primary tumor vasculature, circulating tumor cells, and metastatic lung foci. Combined, these results demonstrate the importance of Mdm2 in orchestrating the initial stages of migration and metastasis.

Original languageEnglish (US)
Pages (from-to)1598-1607
Number of pages10
JournalMolecular Cancer Research
Volume15
Issue number11
DOIs
StatePublished - Nov 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Hauck, P. M., Wolf, E. R., Olivos, D. J., Batuello, C. N., McElyea, K. C., McAtarsney, C. P., Cournoyer, R. M., Sandusky, G. E., & Mayo, L. D. (2017). Early-stage metastasis requires Mdm2 and not p53 gain of function. Molecular Cancer Research, 15(11), 1598-1607. https://doi.org/10.1158/1541-7786.MCR-17-0174