Abstract

Brain metastasis represents an-end stage of breast cancer progression, particularly in patients with triple-negative breast cancer (TNBC), a subtype characterized by aggressive behavior and limited therapeutic options. Successful colonization of the brain requires circulating tumor cells to adhere to and cross the blood-brain barrier (BBB), a tightly regulated endothelial interface that normally restricts cellular infiltration.

Matrix metalloproteinase-1 (MMP-1) has been implicated in endothelial barrier remodeling and tumor cell extravasation; however, the molecular mechanisms governing its dysregulation in metastatic TNBC remain incompletely understood. In this study, we investigated regulatory mechanisms controlling MMP-1 expression in TNBC cells and examined their impact on cancer cell interaction with brain endothelial monolayers.

We demonstrate that highly brain-metastatic TNBC cells exhibit enhanced MMP-1 expression accompanied by increased transmigration across brain endothelial cells and compromised barrier integrity. Mechanistically, loss of a specific tumor-suppressive microRNA was identified as a key upstream event driving MMP-1 upregulation. Restoration of this regulatory pathway suppressed MMP-1 levels, reduced tumor cell transmigration, and preserved endothelial barrier function.

These findings highlight epigenetic mechanisms that governs protease-mediated BBB disruption in TNBC. Targeting this regulatory axis may provide a novel therapeutic strategy to limit brain metastatic dissemination in high-risk breast cancer patients.

Biography

Dr Rania Harati is Associate Professor at the College of Pharmacy, University of Sharjah, United Arab Emirates. She earned her PhD in Experimental and Clinical Pharmacology from Paris-Sud University (Paris-Saclay University) and completed her postdoctoral training at Pierre and Marie Curie University (Sorbonne University) in Paris, France. Her research focuses on understanding the regulation of the blood-brain barrier in health and disease.