2. Academic Validation
  3. Tumor suppressor KEAP1 promotes HSPA9 degradation, controlling mitochondrial biogenesis in breast cancer

Tumor suppressor KEAP1 promotes HSPA9 degradation, controlling mitochondrial biogenesis in breast cancer

  • Cell Rep. 2024 Jul 23;43(7):114507. doi: 10.1016/j.celrep.2024.114507.
Bing Han 1,  Fang Zhen 1,  Yue Sun 1,  Bin Sun 2,  Hong-Yi Wang 1,  Wei Liu 1,  Jian Huang 1,  Xiao Liang 3,  Ya-Ru Wang 1,  Xue-Song Chen 4,  Shui-Jie Li 5,  Jing Hu 6
Affiliations

Affiliations

  • 1 Department of Breast Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, 150 Haping Road, Harbin, Heilongjiang Province 150040, China.
  • 2 Research Center for Pharmacoinformatics (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, 157 Baojian Road, Harbin, Heilongjiang Province 150081, China.
  • 3 Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang Province 150081, China.
  • 4 Department of Oncology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang Province 150001, China. Electronic address: cxs1978@ems.hrbmu.edu.cn.
  • 5 State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang Province 150081, China. Electronic address: shuijie.li@hrbmu.edu.cn.
  • 6 Department of Breast Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, 150 Haping Road, Harbin, Heilongjiang Province 150040, China; Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang Province 150081, China. Electronic address: hujing@ems.hrbmu.edu.cn.
PMID: 39003742 DOI: 10.1016/j.celrep.2024.114507
Abstract

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.

Keywords

CP: Cancer; CP: Cell biology.

Figures
Products
Inhibitors & Agonists
Other Products