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Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer.
Zhang, Yanchao; Zhao, Guomeng; Yu, Liting; Wang, Xindong; Meng, Yao; Mao, Jinlei; Fu, Ziyi; Yin, Yongmei; Li, Jinyao; Wang, Xun; Guo, Changying.
Afiliação
  • Zhang Y; Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, People's Republic of China.
  • Zhao G; Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, People's Republic of China.
  • Yu L; Institute of Modern Biology, Nanjing University, Nanjing, People's Republic of China.
  • Wang X; Department of Protein and Antibody Engineering, School of Pharmacy, Binzhou Medical University, Yantai, People's Republic of China.
  • Meng Y; School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
  • Mao J; School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
  • Fu Z; School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
  • Yin Y; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing People's Hospital, Nanjing, People's Republic of China.
  • Li J; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing People's Hospital, Nanjing, People's Republic of China. ym.yin@hotmail.com.
  • Wang X; Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, People's Republic of China. ljyxju@xju.edu.cn.
  • Guo C; Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. wangxun301gdwk@163.com.
Br J Cancer ; 129(10): 1679-1691, 2023 11.
Article em En | MEDLINE | ID: mdl-37731021
BACKGROUND: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. METHODS: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation. The motility and invasiveness of breast cancer cells were examined in vitro using wound healing and transwell invasion assays. The orthotopic spontaneous metastasis and intra-venous experimental metastasis assays were used to test the formation of metastasis in vivo, respectively. RESULTS: HSP90α interacts with NME1 and increases NME1 lifetime by impeding its ubiquitin-proteasome-mediated degradation. HSP90α overexpression significantly inhibits the metastatic potential of breast cancer cells in vitro and in vivo. A novel cell-permeable peptide, OPT22 successfully mimics the HSP90α function and prolongs the life span of endogenous NME1, resulting in reduced metastasis of breast cancer. CONCLUSION: These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Proteínas de Choque Térmico Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Proteínas de Choque Térmico Idioma: En Ano de publicação: 2023 Tipo de documento: Article