He De, Cui Weiheng, Pang Xijiao, Dong Jiale, Qiu Quanwei, Dong Hongmei, Zhao Ruijun
Department of Thyroid and Breast Surgery, PingXiang People's Hospital, PingXiang, China.
Institute of Precision Cancer Medicine and Pathology, Department of Pathology, School of Medicine, Jinan University, Guangzhou, China.
Sci Rep. 2025 Jun 6;15(1):19986. doi: 10.1038/s41598-025-04500-8.
Breast cancer is a prevalent and deadly disease affecting women worldwide. Recent studies have shown that γ-glutamyl cyclotransferase (GGCT), an enzyme involved in glutathione metabolism, is consistently upregulated in various cancers. However, its specific role in breast cancer remains poorly understood. This study aimed to investigate the functional role of GGCT in breast cancer. Bioinformatics, immunohistochemistry and immunoblotting analysis revealed that GGCT is significantly upregulated in breast cancer tissues, and its high expression is associated with poor survival outcomes. The knockdown of GGCT significantly suppressed MCF-7 and SKBR-3 cell activities. Cell proliferation decreased by 29.4-45.9%, and colony formation reduced by 51.5-56.6%. Migratory ability diminished by 36.8-49.1%, while invasion capability declined by 35.2-55.0%. Moreover, GGCT silencing reduced epithelial-mesenchymal transition (EMT) and inhibited the PI3K/AKT/mTOR signaling pathway. Notably, E-cadherin expression significantly increased in MCF-7 and SKBR-3-shGGCT cells, with changes ranging from 2.1-fold to 5.4-fold. Conversely, N-cadherin expression decreased by 54.2-84.2% in both cell lines. Vimentin expression also decreased significantly, with reductions of 58.8-83.0%. Further analyses indicated that p-AKT expression in MCF-7 and SKBR-3-shGGCT cells decreased by 51.4-84.8%. Additionally, p-mTOR expression was reduced by 71.2-87.2% in both cell lines, compared to shCtrl. Our data highlights the crucial role of GGCT in regulating EMT and the progression of breast cancer. The findings suggest that GGCT not only serves as a valuable prognostic marker but also represents a potential target for therapeutic interventions in breast cancer patients.
乳腺癌是一种在全球范围内影响女性的常见且致命的疾病。最近的研究表明，γ-谷氨酰环转移酶（GGCT）作为一种参与谷胱甘肽代谢的酶，在各种癌症中持续上调。然而，其在乳腺癌中的具体作用仍知之甚少。本研究旨在探讨GGCT在乳腺癌中的功能作用。生物信息学、免疫组织化学和免疫印迹分析表明，GGCT在乳腺癌组织中显著上调，其高表达与不良生存结果相关。敲低GGCT可显著抑制MCF-7和SKBR-3细胞活性。细胞增殖减少了29.4 - 45.9%，集落形成减少了51.5 - 56.6%。迁移能力下降了36.8 - 49.1%，而侵袭能力下降了35.2 - 55.0%。此外，GGCT沉默减少了上皮-间质转化（EMT）并抑制了PI3K/AKT/mTOR信号通路。值得注意的是，E-钙黏蛋白在MCF-7和SKBR-3-shGGCT细胞中的表达显著增加，变化范围为2.1倍至5.4倍。相反，两种细胞系中N-钙黏蛋白的表达均下降了54.2 - 84.2%。波形蛋白的表达也显著下降，减少了58.8 - 83.0%。进一步分析表明，MCF-7和SKBR-3-shGGCT细胞中p-AKT的表达下降了51.4 - 84.8%。此外，与shCtrl相比，两种细胞系中p-mTOR的表达均下降了71.2 - 87.2%。我们的数据突出了GGCT在调节EMT和乳腺癌进展中的关键作用。研究结果表明，GGCT不仅是一个有价值的预后标志物，而且是乳腺癌患者治疗干预的潜在靶点。
