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Updated: Oct 25, 2025

Establishing 3D Endometrial Organoids from the Mouse Uterus
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Tumor Promoting Effect of BMP Signaling in Endometrial Cancer

Tomohiko Fukuda1, Risa Fukuda1, Kohei Miyazono1,2

  • 1Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Box 582, Uppsala University, SE-751 23 Uppsala, Sweden.

International Journal of Molecular Sciences
|August 7, 2021
PubMed

Insights

Bone morphogenetic protein (BMP) signaling promotes endometrial cancer (EC) growth and migration. BMP antagonists like TWSG1 may offer therapeutic potential, particularly when combined with chemotherapy for EC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Bone morphogenetic proteins (BMPs) are part of the transforming growth factor-β (TGF-β) superfamily.
  • The role of BMP signaling in endometrial cancer (EC) remains largely unknown.
  • Investigating BMPs and their antagonists in EC is crucial for understanding tumorigenesis.

Purpose of the Study:

  • To investigate the effects of BMP2 and the BMP antagonist TWSG1 in endometrial cancer (EC).
  • To analyze BMP signaling pathways in EC patient datasets.
  • To explore the therapeutic potential of targeting BMP signaling in EC.

Main Methods:

  • Analysis of TCGA and MSK-IMPACT datasets for gene mutations and expression.
  • In vitro studies using Ishikawa EC cells and ovarian cancer cell lines.
  • Stimulation with BMP2 and BMP7, and treatment with BMP inhibitor LDN193189 and carboplatin.

Main Results:

  • EC patients showed frequent ACVR1 mutations and high BMP ligand/receptor expression.
  • BMP2 enhanced EC cell sphere formation (via c-KIT) and migration (via SLUG), inducing epithelial-mesenchymal transition (EMT).
  • TWSG1 suppressed BMP7-induced, but not BMP2-induced, sphere formation and migration.

Conclusions:

  • BMP signaling appears to promote EC tumorigenesis and progression.
  • TWSG1 acts as a BMP7 antagonist in EC.
  • Combining BMP signaling inhibitors with chemotherapy may be a viable treatment strategy for EC.
Keywords:
ACVR1BMPEMTcancer stem cellsendometrial cancer

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