Brown Adipocyte Promotes HR+ Breast Cancer Invasiveness Through IRX3-Mediated Mitochondrial Dysfunction

Area of Science:

• Oncology
• Cell Biology
• Metabolic Research

Background:

• Adipocytes are crucial components of the breast cancer tumor microenvironment.
• The precise mechanisms by which adipocytes influence breast cancer progression are not fully understood.

Purpose of the Study:

• To investigate the role of adipocytes in luminal A breast cancer cell invasiveness.
• To elucidate the cellular and molecular mechanisms involved.

Main Methods:

• Co-culture of MCF7 breast cancer cells with various adipocyte types.
• Assessment of invasiveness through proliferation, migration, and invasion assays.
• Analysis of morphological, cellular, and molecular alterations.
• In vivo studies using an orthotopic breast cancer xenograft mouse model.

Main Results:

• Co-culture with adipocytes, particularly brown adipocytes (BAC), significantly increased MCF7 cell invasiveness and tumorigenic potential.
• BAC co-culture promoted MCF7 proliferation, epithelial-mesenchymal transition (EMT), and stemness.
• Upregulation of IRX3, a gene related to adipogenesis and mitochondrial dynamics, was observed.
• IRX3 knockdown normalized mitochondrial function and reduced cancer cell invasiveness and tumor growth.

Conclusions:

• Brown adipocytes promote breast cancer invasiveness via upregulation of adipogenesis-related IRX3.
• IRX3 exerts its effects by regulating mitochondrial function.
• Targeting IRX3 offers a potential therapeutic strategy for luminal A breast cancer.