Department of General Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226000, China.
Breast Cancer Res. 2024 Sep 19;26(1):135. doi: 10.1186/s13058-024-01892-9.
Breast cancer is common worldwide. Phosphoglycerate mutase 5 (PGAM5) belongs to the phosphoglycerate mutase family and plays an important role in many cancers. However, research on its role in breast cancer remains unclear. The present investigation highlights the significant expression of PGAM5 in breast cancer and its essential role in cell proliferation, invasion, apoptosis and the regulation of ferroptosis in breast cancer cells. Overexpression or knockdown of ubiquitin-specific protease 11 (USP11) promotes or inhibits the growth and metastasis of breast cancer cells, respectively, in vitro and in vivo. Mechanistically, USP11 stabilizes PGAM5 via de-ubiquitination, protecting it from proteasome-mediated degradation. In addition, the USP11/PGAM5 complex promotes breast cancer progression by activating iron death-related proteins, indicating that the synergy between USP11 and PGAM5 may serve as a predictor of disease outcome and provide a new treatment strategy for breast cancer.
乳腺癌是一种常见的全球疾病。磷酸甘油酸变位酶 5（PGAM5）属于磷酸甘油酸变位酶家族，在许多癌症中发挥着重要作用。然而，其在乳腺癌中的作用研究仍不清楚。本研究强调了 PGAM5 在乳腺癌中的显著表达及其在乳腺癌细胞增殖、侵袭、凋亡和铁死亡调控中的重要作用。在体外和体内，泛素特异性蛋白酶 11（USP11）的过表达或敲低分别促进或抑制乳腺癌细胞的生长和转移。从机制上讲，USP11 通过去泛素化稳定 PGAM5，使其免受蛋白酶体介导的降解。此外，USP11/PGAM5 复合物通过激活铁死亡相关蛋白促进乳腺癌的进展，表明 USP11 和 PGAM5 之间的协同作用可能作为疾病结果的预测因子，并为乳腺癌提供一种新的治疗策略。
