TargetingFoxM1EffectivelyRetardsp53-NullLymphomaand Sarcoma

The forkhead box transcription factor FOXM1 is considered to be a promising target for cancer therapy. However,thesignificanceofFOXM1intumorsharboringmutationinp53,whichisverycommon,isunclear.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 genessurvivinand Bmi1.AnARF-derivedpeptidethatinhibitstheactivityofFOXM1,bytargetingittothenucleolus,alsoinduces 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 sarcomaandlymphomacarryinglossoffunctionmutationinp53.MolCancerTher;12(5);759–67. � 2013AACR.