FOXM1 regulates glycolysis and energy production in multiple myeloma

Yan Cheng, Fumou Sun, Krista Thornton, Xuefang Jing, Jing Dong, Grant Yun, Michael Pisano, Fenghuang Zhan, Sung Hoon Kim, John A. Katzenellenbogen, Benita S. Katzenellenbogen, Parameswaran Hari, Siegfried Janz

Research output: Contribution to journalArticlepeer-review


The transcription factor, forkhead box M1 (FOXM1), has been implicated in the natural history and outcome of newly diagnosed high-risk myeloma (HRMM) and relapsed/refractory myeloma (RRMM), but the mechanism with which FOXM1 promotes the growth of neoplastic plasma cells is poorly understood. Here we show that FOXM1 is a positive regulator of myeloma metabolism that greatly impacts the bioenergetic pathways of glycolysis and oxidative phosphorylation (OxPhos). Using FOXM1-deficient myeloma cells as principal experimental model system, we find that FOXM1 increases glucose uptake, lactate output, and oxygen consumption in myeloma. We demonstrate that the novel 1,1-diarylethylene small-compound FOXM1 inhibitor, NB73, suppresses myeloma in cell culture and human-in-mouse xenografts using a mechanism that includes enhanced proteasomal FOXM1 degradation. Consistent with the FOXM1-stabilizing chaperone function of heat shock protein 90 (HSP90), the HSP90 inhibitor, geldanamycin, collaborates with NB73 in slowing down myeloma. These findings define FOXM1 as a key driver of myeloma metabolism and underscore the feasibility of targeting FOXM1 for new approaches to myeloma therapy and prevention.

Original languageEnglish (US)
Pages (from-to)3899-3911
Number of pages13
Issue number32
StatePublished - Aug 5 2022

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Cancer Research


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