Chien Yi-Chung, Wu Jia-Yan, Pang Chi-Chun, Chou Ruey-Hwang, Yu Yung-Luen
Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 406040, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan.
J Cancer. 2025 Jan 13;16(4):1296-1309. doi: 10.7150/jca.104000. eCollection 2025.
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.
乳腺癌仍然是全球女性癌症相关死亡的主要原因。降低乳腺癌死亡率的一个重大挑战是多药耐药性。这种耐药性通过多种机制产生，如药物外排增加、DNA修复改善、逃离衰老、表观遗传修饰、肿瘤异质性、肿瘤微环境（TME）改变以及上皮-间质转化（EMT）。这些因素共同使得克服耐药性特别困难。因此，在本研究中，我们分析了癌症基因组图谱（TCGA）的数据，并鉴定出一个新基因——半乳糖凝集素-8，它在乳腺癌进展中起关键调节作用。基因集富集分析（GSEA）进一步表明半乳糖凝集素-8参与调节乳腺癌的耐药性。为了验证这一发现，我们进行了一项大规模分析，将耐药三阴性乳腺癌（TNBC）细胞系与对照组进行比较。我们的结果表明，耐药细胞中半乳糖凝集素-8的表达显著增加，差异具有统计学意义。此外，我们发现降低耐药细胞系中半乳糖凝集素-8的表达不仅恢复了抗癌药物的有效性，还抑制了肿瘤细胞的增殖和迁移。因此，我们的发现突出了半乳糖凝集素-8显著的预后和治疗潜力，强调了未来研究探索乳腺癌靶向治疗策略的重要性。
