Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, 613 West of Huangpu Avenue, Guangzhou, 510630, China.
Department of Breast Medicine, Foshan Women and Children Hospital, Foshan, 528000, China.
Hum Cell. 2024 Oct 18;38(1):1. doi: 10.1007/s13577-024-01137-z.
Sialyltransferases are enzymes that play a crucial role in regulating cancer progression by modifying glycoproteins through sialylation. In particular, the ST3 beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) enzyme is known to be upregulated in breast cancer, but its specific biological functions have not been fully understood. This study aimed to investigate the impact and mechanisms of ST3GAL4 on aerobic glycolysis in breast cancer. We examined ST3GAL4 expression in tumor tissue samples and breast cancer cell lines and also manipulated ST3GAL4 expression in breast cancer cells using lentivirus transduction. The study evaluated cellular processes such as cell viability, cell cycle progression, and aerobic glycolysis by measuring parameters like extracellular acidification rate, glucose uptake, lactate production, and lactate dehydrogenase A (LDHA) expression. We found that ST3GAL4 expression was consistently increased in tumor tissues and breast cancer cell lines. High ST3GAL4 expression was associated with a poor prognosis for patients with breast cancer. Inhibiting ST3GAL4 expression decreased cell viability, disrupted cell cycle progression, and reduced aerobic glycolysis and LDHA expression. Furthermore, suppressing ST3GAL4 expression in animal models reduced tumor growth and cell proliferation. Conversely, overexpressing ST3GAL4 promoted cell viability and cell cycle progression, but these effects were reversed when an inhibitor of aerobic glycolysis was used. The study provided evidence in cells and animal models that ST3GAL4 promotes tumorigenesis in breast cancer by enhancing aerobic glycolysis. These findings suggest that targeting ST3GAL4 may be a potential strategy for the treatment of breast cancer.
唾液酸转移酶是通过唾液酸化修饰糖蛋白来调节癌症进展的关键酶。特别是 ST3β-半乳糖苷α-2,3-唾液酸转移酶 4（ST3GAL4）酶在乳腺癌中被上调，但它的具体生物学功能尚未完全理解。本研究旨在探讨 ST3GAL4 对乳腺癌有氧糖酵解的影响及其机制。我们检测了肿瘤组织样本和乳腺癌细胞系中的 ST3GAL4 表达，并使用慢病毒转导来操纵乳腺癌细胞中的 ST3GAL4 表达。该研究通过测量细胞外酸化率、葡萄糖摄取、乳酸生成和乳酸脱氢酶 A（LDHA）表达等参数来评估细胞活力、细胞周期进展和有氧糖酵解等细胞过程。我们发现 ST3GAL4 表达在肿瘤组织和乳腺癌细胞系中持续增加。高 ST3GAL4 表达与乳腺癌患者的预后不良相关。抑制 ST3GAL4 表达降低了细胞活力，破坏了细胞周期进展，并减少了有氧糖酵解和 LDHA 表达。此外，在动物模型中抑制 ST3GAL4 表达减少了肿瘤生长和细胞增殖。相反，过表达 ST3GAL4 促进了细胞活力和细胞周期进展，但当使用有氧糖酵解抑制剂时，这些效应被逆转。该研究在细胞和动物模型中提供了证据，表明 ST3GAL4 通过增强有氧糖酵解促进乳腺癌的肿瘤发生。这些发现表明，靶向 ST3GAL4 可能是治疗乳腺癌的一种潜在策略。
