Work

Metformin Inhibits Cell Motility and Proliferation of Triple-Negative Breast Cancer Cells by Blocking HMGB1/RAGE Signaling

Year: 2025

Type: article

Abstract: High-mobility group box 1 (HMGB1) is a nuclear chromatin protein overexpressed in various cancers and linked to tumor progression. Outside the cell, HMGB1 binds to receptors such as the receptor for advanced glycation end products (RAGE), promoting metastasis. Targeting this signaling pathway may provide a new therapeutic strategy for aggressive cancers. Metformin, a well-established antidiabetic drug, directly interacts with HMGB1, inhibiting its pro-inflammatory functions. This study investigates metformin's effects on the HMGB1/RAGE signaling pathway in triple-negative breast cancer (TNBC) cells. Using wound-healing and colony formation assays, we demonstrate that metformin reduces HMGB1-induced cell migration and proliferation. Immunoblotting and immunofluorescence analyses reveal that metformin decreases RAGE stabilization on the cell membrane, disrupts NF-κB signaling, and reverses the epithelial-to-mesenchymal transition (EMT) by increasing E-cadherin, reducing vimentin, and stabilizing β-catenin at the cell membrane. Furthermore, metformin lowers HMGB1 and RAGE protein levels, disrupting the positive feedback loop that promotes cancer aggressiveness. These findings highlight metformin's potential as a therapeutic agent in TNBC by inhibiting HMGB1/RAGE-driven metastasis.

Source: Cells

DOI: 10.3390/cells14080590

Authors: Shazie Yusein-Myashkova, Desislava Vladimirova, Anastas Gospodinov, Iva Ugrinova, Jordana Todorova

Institutions: Bulgarian Academy of Sciences, Institute of Molecular Biology

Language: English

Topic: Advanced Glycation End Products research

Subfield: Clinical Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258