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FOXM1 promotes neurofibromatosis type 1-associated malignant peripheral nerve sheath tumor progression in a

Rehanguli Aimaier1, Man-Hon Chung1, Yihui Gu1

  • 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cancer Gene Therapy
|July 24, 2023
PubMed

Insights

Forkhead box M1 (FOXM1) drives malignant peripheral nerve sheath tumor (MPNST) progression by increasing NUF2 expression. Targeting the FOXM1-NUF2 pathway offers a potential therapeutic strategy for these aggressive sarcomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas with poor prognosis and limited treatment options.
  • Understanding the molecular drivers of MPNSTs is crucial for developing targeted therapies.
  • Forkhead box M1 (FOXM1) is implicated in various cancers, but its role in MPNSTs is not well-defined.

Purpose of the Study:

  • To investigate the role of FOXM1 in MPNST progression.
  • To identify downstream targets of FOXM1 in MPNSTs.
  • To evaluate the FOXM1-NUF2 axis as a potential therapeutic target.

Main Methods:

  • Analysis of Gene Expression Omnibus (GEO) datasets and tissue microarrays.
  • In vitro studies involving FOXM1 overexpression and knockdown in MPNST cells.
  • Bioinformatics analysis and luciferase reporter assays to identify FOXM1 targets.
  • In vitro and in vivo experiments to validate the FOXM1-NUF2 interaction.

Main Results:

  • FOXM1 upregulation was significantly associated with poor prognosis in MPNST patients.
  • FOXM1 modulated MPNST cell proliferation and colony formation.
  • NUF2 was identified as a direct downstream target of FOXM1.
  • FOXM1-induced MPNST cell proliferation was dependent on elevated NUF2 expression, and NUF2 knockdown abrogated this effect.

Conclusions:

  • The FOXM1-NUF2 signaling axis plays a critical role in mediating human MPNST progression.
  • Targeting the FOXM1-NUF2 pathway represents a promising therapeutic strategy for MPNSTs.

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