氧化应激相关蛋白 Kelch 样 ECH 相关蛋白 1 (KEAP1) 是 E3 泛素连接酶的底物连接子，在蛋白质的泛素化修饰中发挥重要作用。然而，KEAP1在乳腺癌中的功能及其对乳腺癌患者生存的影响仍不清楚。我们的研究表明，KEAP1 作为一种积极的预后因子，在调节乳腺癌细胞增殖、凋亡和细胞周期转变中发挥着至关重要的作用。我们利用人类肿瘤组织、高通量检测技术和小鼠异种移植肿瘤模型研究其潜在机制。 KEAP1 是细胞代谢的关键调节因子，其重编程是肿瘤发生的标志之一。 KEAP1 通过调节 HSPA9 泛素化和降解对线粒体生物发生和氧化磷酸化具有显着影响。这些结果表明 KEAP1 可以作为乳腺癌治疗的潜在生物标志物和治疗靶点。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

The oxidative-stress-related protein Kelch-like ECH-associated protein 1 (KEAP1) is a substrate articulator of E3 ubiquitin ligase, which plays an important role in the ubiquitination modification of proteins. However, the function of KEAP1 in breast cancer and its impact on the survival of patients with breast cancer remain unclear. Our study demonstrates that KEAP1, a positive prognostic factor, plays a crucial role in regulating cell proliferation, apoptosis, and cell cycle transition in breast cancer. We investigate the underlying mechanism using human tumor tissues, high-throughput detection technology, and a mouse xenograft tumor model. KEAP1 serves as a key regulator of cellular metabolism, the reprogramming of which is one of the hallmarks of tumorigenesis. KEAP1 has a significant effect on mitochondrial biogenesis and oxidative phosphorylation by regulating HSPA9 ubiquitination and degradation. These results suggest that KEAP1 could serve as a potential biomarker and therapeutic target in the treatment of breast cancer.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.