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Updated: Aug 19, 2025

Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
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Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas

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PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets

Nebeyu Yosef Gizaw1, Pauliina Kallio2, Tatjana Punger1

  • 1Stem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland.

Proceedings of the National Academy of Sciences of the United States of America
|December 2, 2022
PubMed

Insights

The transcription factor PROX1 drives pediatric rhabdomyosarcoma (RMS) growth. Inhibiting fibroblast growth factor receptors (FGFR) offers a potential new therapy for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pediatric Cancer Research

Background:

  • Rhabdomyosarcoma (RMS) is an aggressive pediatric soft-tissue cancer with poor survival rates.
  • Current RMS therapies have severe long-term side effects, necessitating novel treatment strategies.

Purpose of the Study:

  • To investigate the role of the prospero-related homeobox 1 (PROX1) transcription factor in RMS development and growth.
  • To identify potential therapeutic targets for RMS based on PROX1's function.

Main Methods:

  • Assessed PROX1 expression in RMS tumors.
  • Utilized PROX1 gene silencing to study its effects on RMS cell behavior.
  • Analyzed transcriptomic changes following PROX1 silencing.
  • Investigated the role of fibroblast growth factor receptors (FGFR) in mediating PROX1's effects.

Main Results:

  • PROX1 is highly expressed in RMS tumors across different origins.
  • PROX1 is essential for RMS cell clonogenicity, growth, and tumor formation.
  • PROX1 silencing reversed RMS cell characteristics towards benign mesenchymal stem cells.
  • Fibroblast growth factor receptors (FGFR) mediate PROX1's growth-promoting effects in RMS.
  • A pan-FGFR inhibitor effectively suppressed RMS cell proliferation and induced apoptosis.

Conclusions:

  • PROX1 plays a critical role in regulating RMS development and progression.
  • Targeting FGFR with pan-FGFR inhibitors presents a promising therapeutic avenue for RMS.
  • This research offers a potential alternative treatment option for pediatric rhabdomyosarcoma.
Keywords:
FGFRPROX1cancermyogenesissarcoma

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