Targeting FoxM1 effectively retards p53-null lymphomaand sarcoma

Zebin Wang, Yu Zheng, Hyun Jung Park, Jing Li, Janai R. Carr, Yi Ju Chen, Megan M. Kiefer, Dragana Kopanja, Srilata Bagchi, Angela L. Tyner, Pradip Raychaudhuri

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The forkhead box transcription factor FOXM1 is considered to be a promising target for cancer therapy. However, the significance of FOXM1 in tumors harboring mutation in p53, which is very common, is unclear. In this study, we investigated the efficacy of FoxM1 targeting in spontaneous p53-null tumors using genetic ablation as well as using a peptide inhibitor of FOXM1. We show that conditional deletion of FoxM1 inhibits growth of the p53-null thymic lymphoma and sarcoma cells. In addition, deletion of FoxM1 induces apoptotic cell death of the p53-null tumors, accompanied by reduced expression of the FOXM1 target genes survivin and Bmi1. AnARF-derived peptide that inhibits the activity of FOXM1, by targeting it to the nucleolus, also induces apoptosis in the p53-null sarcoma and lymphoma, leading to a strong inhibition of their metastatic colonization. Together, our observations suggest that FOXM1 is critical for survival and growth of the p53-null lymphoma and sarcoma and provide proof-of-principle that FOXM1 is an effective therapeutic target for sarcoma and lymphoma carrying loss of function mutation in p53.

Original languageEnglish (US)
Pages (from-to)759-767
Number of pages9
JournalMolecular Cancer Therapeutics
Volume12
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wang, Z., Zheng, Y., Park, H. J., Li, J., Carr, J. R., Chen, Y. J., Kiefer, M. M., Kopanja, D., Bagchi, S., Tyner, A. L., & Raychaudhuri, P. (2013). Targeting FoxM1 effectively retards p53-null lymphomaand sarcoma. Molecular Cancer Therapeutics, 12(5), 759-767. https://doi.org/10.1158/1535-7163.MCT-12-0903