Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression

H. Kim, Kyung-Jae Park, B. K. Ryu, Dong-Hyuk Park, D. S. Kong, K. Chong, Yang Seok Chae, Yong Gu Chung, S. I. Park, Shin-Hyuk Kang

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Aims: Aggressive meningioma remains incurable with neither chemo- nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. Methods: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. Results: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of β-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. Conclusions: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.

Original languageEnglish
Pages (from-to)125-141
Number of pages17
JournalNeuropathology and Applied Neurobiology
Issue number2
Publication statusPublished - 2020 Feb 1

Bibliographical note

Funding Information:
Korea University Research Grants (S.I.P. and S.-H.K); the National Cancer Centre of Korea (HA17C0040 to S.I.P.); the National Research Foundation, the Ministries of Health and Welfare, and of Science and ICT, the Republic of Korea (2013R1A1A1006032 to K.-J.P., 2014R1A2A2A01005274 and 2017R1D1A1B03034199 to S.-H.K., and 2015R1C1A1A01051508 and 2018R1D1A1B07050329 to S.I.P.).

Publisher Copyright:
© 2019 British Neuropathological Society

Copyright 2020 Elsevier B.V., All rights reserved.


  • FOXM1
  • brain tumour
  • meningioma
  • progression
  • siomycin A

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)


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