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Updated: Feb 28, 2026

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Autocrine BMP-4 Signaling Is a Therapeutic Target in Colorectal Cancer

Yuichiro Yokoyama1,2, Toshiaki Watanabe2, Yusuke Tamura1

  • 1Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Cancer Research
|June 15, 2017
PubMed

Insights

Targeting bone morphogenetic protein 4 (BMP-4) may offer a new treatment for colorectal cancer. Inhibiting BMP-4 signaling in cancer cells triggered apoptosis and reduced tumor formation in mice.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Colorectal cancer (CRC) with metastatic lesions has a poor prognosis, necessitating novel targeted therapies.
  • Bone morphogenetic protein 4 (BMP-4) is frequently upregulated in CRC, leading to activated BMP signaling pathways.

Purpose of the Study:

  • To investigate the role of BMP-4 signaling in colorectal cancer progression.
  • To evaluate the therapeutic potential of inhibiting BMP-4 signaling in colorectal cancer.

Main Methods:

  • Analysis of BMP-4 expression in human colorectal cancer cells and tissues.
  • Treatment of colorectal cancer cells with the BMP type I receptor inhibitor LDN-193189.
  • Assessment of apoptosis induction via Erk MAPK dephosphorylation.
  • Evaluation of tumor formation in mice treated with LDN-193189.

Main Results:

  • BMP-4 expression and signaling are universally activated in colorectal cancer.
  • LDN-193189 treatment increased DUSP5 phosphatase expression, inducing apoptosis through Erk MAPK dephosphorylation.
  • Administration of LDN-193189 significantly reduced colorectal cancer cell tumor formation in vivo.

Conclusions:

  • Inhibition of autocrine BMP-4 signaling is a promising therapeutic strategy for colorectal cancer.
  • Targeting BMP-4 may overcome poor prognoses associated with metastatic colorectal cancer.

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