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FOXM1 regulates glycolysis and energy production in multiple myeloma. Oncogene 2022 Aug;41(32):3899-3911



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-85133568311 (requires institutional sign-in at Scopus site)   13 Citations


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.

Author List

Cheng Y, Sun F, Thornton K, Jing X, Dong J, Yun G, Pisano M, Zhan F, Kim SH, Katzenellenbogen JA, Katzenellenbogen BS, Hari P, Janz S


Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Line, Tumor
Cell Proliferation
Forkhead Box Protein M1
Forkhead Transcription Factors
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
Multiple Myeloma
Transcription Factors