Beige Adipocytes Promote Triple‐Negative Breast Cancer Cell Migration and Malignancy Through BMP4 Signaling
Year: 2025
Type: article
Abstract: ABSTRACT Breast cancer remains a leading cause of cancer‐related mortality among women, with adipocyte–breast cancer interactions playing a critical role in cancer progression. Mammary gland fat contains both white and brown‐like adipocytes. While white adipocytes have been associated with aggressive tumor behavior, the impact of brown‐like adipocytes on cancer progression remains largely unclear. This study investigated the roles of beige (UCP1 high ) and white (UCP1 low ) adipocytes derived from human adipose‐derived mesenchymal stem cells within the tumor microenvironment. Triple‐negative breast cancer (TNBC) MDA‐MB‐231 cells exhibited increased migration and invasion when exposed to white (hWCM) or beige (hBCM) adipocyte‐conditioned medium, with a more pronounced effect observed with hBCM. Mechanistically, beige adipocytes secreted significantly higher levels of bone morphogenetic protein 4 (BMP4) compared to white adipocytes, which enhanced TNBC cell migration. Inhibition of BMP signaling with Noggin effectively reduced the migration and malignancy of MDA‐MB‐231 cells induced by hBCM, underscoring the pivotal role of BMP4 in breast cancer progression. Furthermore, an ex vivo model using primary mature adipocytes revealed that co‐culturing MDA‐MB‐231 cells with UCP1 high adipocytes from cold‐exposed mice increased cell migration and altered epithelial‐mesenchymal transition gene expression compared to UCP1 low adipocytes from room temperature‐housed mice. These findings highlight the critical role of UCP1 high beige adipocytes and BMP4 signaling in TNBC progression, suggesting that targeting BMP4 signaling may offer a novel therapeutic strategy for managing TNBC.
Source: The FASEB Journal
Authors: Ying‐Fang Chen, Chung‐Lin Jiang, Chi‐Ling Tan, Pei‐Hsiang Lai, Fu‐Jung Lin
Institution: National Taiwan University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410190842