HSPD1 Supports Osteosarcoma Progression through Stabilizing ATP5A1 and thus Activation of AKT/mTOR Signaling

作者：Yiming Zhang, Ruilin Pan, Kun Li, Lek Hang Cheang, Jing Zhao, Zhangfeng Zhong, Shao-Ping Li, Jinghao Wang, Xiaofang Zhang, Yanmei Cheng, Xiaofei Zheng, Rong‐Rong He, Huajun Wang · 发表于：International Journal of Biological Sciences · 年份：2024 · DOI：10.7150/ijbs.100015 · 被引用次数：11 · 研究领域：Biochemical and Molecular Research、ATP Synthase and ATPases Research、MicroRNA in disease regulation

experiments, we systematically identified HSPD1 as an important contributor to the regulation of proliferation, metastasis, and apoptosis in osteosarcoma by promoting the epithelial-mesenchymal transition (EMT) and activating AKT/mTOR signaling. Subsequently, ATP5A1 was determined as a potential target of HSPD1 using immunoprecipitation followed by mass spectrometry. Mechanistically, HSPD1 may interact with ATP5A1 to reduce the K48-linked ubiquitination and degradation of ATP5A1, which ultimately activates the AKT/mTOR pathway to ensure osteosarcoma progression and EMT process. These findings expand the potential mechanisms by which HSPD1 exerts biological effects and provide strong evidence for its inclusion as a potential therapeutic target in osteosarcoma.