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Related Experiment Video

Updated: May 8, 2025

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Beige Adipocytes Promote Triple-Negative Breast Cancer Cell Migration and Malignancy Through BMP4 Signaling.

Ying-Fang Chen1, Chung-Lin Jiang1, Chi-Ling Tan1

  • 1Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 7, 2025
PubMed
Summary

Beige adipocytes, a type of fat cell, promote triple-negative breast cancer (TNBC) progression by secreting bone morphogenetic protein 4 (BMP4). Targeting BMP4 signaling may offer new TNBC treatment strategies.

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BMP4TNBCbeige adipocytebreast cancertumor microenvironment

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Area of Science:

  • Cell Biology
  • Oncology
  • Endocrinology

Background:

  • Adipocyte-breast cancer interactions influence cancer progression.
  • Mammary fat comprises white and brown-like adipocytes, with unclear roles for the latter in cancer.
  • Triple-negative breast cancer (TNBC) is a particularly aggressive form of breast cancer.

Purpose of the Study:

  • To investigate the role of beige (UCP1high) and white (UCP1low) adipocytes in TNBC progression.
  • To elucidate the mechanisms by which adipocytes affect TNBC cell migration and invasion.
  • To explore potential therapeutic targets for TNBC based on adipocyte signaling.

Main Methods:

  • Differentiated human adipose-derived mesenchymal stem cells into white and beige adipocytes.
  • Treated TNBC MDA-MB-231 cells with conditioned media from these adipocytes.
  • Utilized an ex vivo model with primary adipocytes from cold-exposed and room temperature-housed mice.
  • Measured cell migration, invasion, and gene expression.
  • Investigated the role of bone morphogenetic protein 4 (BMP4) signaling using Noggin inhibitor.

Main Results:

  • Beige adipocyte-conditioned medium (hBCM) significantly increased MDA-MB-231 cell migration and invasion compared to white adipocyte-conditioned medium (hWCM).
  • Beige adipocytes secreted higher levels of BMP4, which enhanced TNBC cell migration.
  • Inhibition of BMP signaling with Noggin reduced hBCM-induced TNBC cell migration and malignancy.
  • Co-culture with UCP1high adipocytes increased MDA-MB-231 cell migration and altered epithelial-mesenchymal transition gene expression.

Conclusions:

  • UCP1high beige adipocytes promote TNBC progression, particularly migration and invasion.
  • BMP4 signaling is a key mechanism mediating the pro-tumorigenic effects of beige adipocytes.
  • Targeting BMP4 signaling presents a potential therapeutic strategy for TNBC.