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The forkhead box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in malignant rhabdoid tumor

Yuichi Shibui1, Kenichi Kohashi1, Akihiko Tamaki1

  • 1Department of Anatomic Pathology Graduate School of Medical Sciences, Kyushu University, Maidashi3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.

Journal of Cancer Research and Clinical Oncology
|November 22, 2020
PubMed
Abstract

Insights

Forkhead box transcription factor 1 (FOXM1) is overexpressed in malignancies. Downregulating FOXM1 in malignant rhabdoid tumor (MRT) cells inhibited proliferation and drug resistance, suggesting FOXM1 as a potential therapeutic target for this aggressive sarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Malignant rhabdoid tumor (MRT) is a rare, aggressive sarcoma with poor prognosis.
  • Novel therapeutic strategies are crucial for improving MRT patient outcomes.
  • Forkhead box transcription factor 1 (FOXM1) is implicated in the pathogenesis of various human cancers.

Purpose of the Study:

  • To investigate the clinicopathological and prognostic significance of FOXM1 expression in MRT.
  • To elucidate the role of FOXM1 in MRT progression and its potential as a therapeutic target.

Main Methods:

  • Immunohistochemistry was used to analyze FOXM1 expression in 23 MRT specimens.
  • Clinicopathological and prognostic analyses were performed.
  • Small interfering RNA (siRNA) and a FOXM1 inhibitor (thiostrepton) were used to downregulate FOXM1 in MRT cell lines.
  • In vitro assays assessed the effects of FOXM1 downregulation on cell proliferation, drug resistance, migration, invasion, cell cycle, and apoptosis.
  • cDNA microarray analysis identified FOXM1-regulated genes involved in DNA damage repair.

Main Results:

  • Primary renal MRTs exhibited significantly lower FOXM1 protein expression.
  • Downregulation of FOXM1 in MRT cell lines via siRNA or thiostrepton inhibited cell proliferation, chemoresistance, migration, and invasion.
  • FOXM1 inhibition induced cell cycle arrest and apoptosis in MRT cell lines.
  • FOXM1 was found to regulate FANCD2 and NBS1, key genes in DNA damage repair pathways.

Conclusions:

  • FOXM1 plays a significant role in the progression of malignant rhabdoid tumors.
  • FOXM1 inhibition demonstrates potential for therapeutic intervention in MRT.
  • FOXM1 represents a promising therapeutic target for malignant rhabdoid tumors.
Keywords:
Cell cycleFANCD2FOXM1Malignant rhabdoid tumorNBS1

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