Your browser doesn't support javascript.
loading
Oxidized ATM governs stemness of breast cancer stem cell through regulating ubiquitylation and acetylation switch.
Zhou, Xinyue; Liu, Xiaoqi; Wan, Xueying; Xu, Ming; Wang, Rui; Yang, Dan; Peng, Meixi; Jin, Ting; Tang, Rui; Liu, Manran; Hou, Yixuan.
Afiliación
  • Zhou X; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Liu X; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China.
  • Wan X; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Xu M; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Wang R; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Yang D; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Peng M; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Jin T; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Tang R; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Liu M; Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • Hou Y; Experimental Teaching Center of Basic Medicine Science, Chongqing Medical University, Chongqing, 400016, China. Electronic address: yixuan_hou@cqmu.edu.cn.
Biochem Biophys Res Commun ; 691: 149243, 2024 Jan 08.
Article en En | MEDLINE | ID: mdl-38016338
Cancer stem cells (CSCs), as parts of tumor initiation cells, play a crucial role to tumorigenesis, development and recurrence. However, the complicated mechanisms of CSCs to adapt to tumor microenvironment and its stemness maintenance remains unclear. Here, we show that oxidized ATM, a hypoxia-activated cytoplasm ATM, acts a novel function to maintain CSC stemness in triple-negative breast cancer cells (BCSCs) via regulating histone H4 acetylation. Mechanistically, oxidized ATM phosphorylates TRIM21 (a E3 ubiquitin ligase) serine 80 and serine 469. Serine 80 phosphorylation of TRIM21 is essential for the ubiquitination activity of TRIM21. TRIM21 binds with SIRT1 (one of deacetylase), resulting in ubiquitylation-mediated degradation of SIRT1. The reduced SIRT1 leads to increase of histone H4 acetylation, thus facilitating CSC-related gene expression. Clinical data verify that high level of ATM in breast tumors is positively correlated with malignant grade, and is closely related with low SIRT1, high p-TRIM21, and high CD44 expression. In conclusion, our study provides a novel mechanism by which oxidized ATM governing BCSCs stemness and reveals an important link among oxidized ATM, histone acetylation, and BCSCs maintenance.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Sirtuina 1 Límite: Female / Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Sirtuina 1 Límite: Female / Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos