The clinical impact of galectin-8 in drug resistant breast cancer

Abstract

Breast cancer remains the leading cause of cancer-related mortality among women globally. A significant challenge in lowering breast cancer death rates is multidrug resistance. This resistance arises through various mechanisms, such as heightened drug efflux, improved DNA repair, escape from senescence, epigenetic modifications, tumor heterogeneity, alterations in the tumor microenvironment (TME), and the epithelial-to-mesenchymal transition (EMT). These factors collectively make overcoming drug resistance particularly difficult. Therefore, in this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a novel gene, galectin-8, which plays a critical regulatory role in breast cancer progression. Gene Set Enrichment Analysis (GSEA) further revealed that galectin-8 is involved in modulating drug resistance in breast cancer. To validate this finding, we conducted a mass assay comparing drug-resistant triple-negative breast cancer (TNBC) cell lines with control groups. Our results demonstrated a significant increase in galectin-8 expression in the drug-resistant cells, with statistically significant differences observed. In addition, we found that reducing galectin-8 expression in drug-resistant cell lines not only reinstated the effectiveness of anticancer drugs but also suppressed tumor cell proliferation and migration. Therefore, our findings highlight the significant prognostic and therapeutic potential of galectin-8, emphasizing the importance of future research to explore targeted therapeutic strategies in breast cancer.