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Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem-like cells.
Cui, Bai; Luo, Yuanyuan; Tian, Pengfei; Peng, Fei; Lu, Jinxin; Yang, Yongliang; Su, Qitong; Liu, Bing; Yu, Jiachuan; Luo, Xi; Yin, Liu; Cheng, Wei; An, Fan; He, Bin; Liang, Dapeng; Wu, Sijin; Chu, Peng; Song, Luyao; Liu, Xinyu; Luo, Huandong; Xu, Jie; Pan, Yujia; Wang, Yang; Li, Dangsheng; Huang, Peng; Yang, Qingkai; Zhang, Lingqiang; Zhou, Binhua P; Liu, Suling; Xu, Guowang; Lam, Eric W-F; Kelley, Keith W; Liu, Quentin.
Afiliación
  • Cui B; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Luo Y; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
  • Tian P; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Peng F; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Lu J; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Yang Y; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Su Q; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
  • Liu B; Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
  • Yu J; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Luo X; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Yin L; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Cheng W; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • An F; Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
  • He B; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Liang D; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Wu S; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
  • Chu P; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Song L; Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
  • Liu X; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Luo H; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Xu J; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
  • Pan Y; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Wang Y; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Li D; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Huang P; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Yang Q; Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Zhang L; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
  • Zhou BP; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • Liu S; State Key Laboratory of Proteomics, National Center of Protein Sciences, Beijing Institute of Lifeomics, Beijing, China.
  • Xu G; Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, College of Medicine, Lexington, Kentucky, USA.
  • Lam EW; Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai, China.
  • Kelley KW; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
  • Liu Q; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
J Clin Invest ; 129(3): 1030-1046, 2019 03 01.
Article en En | MEDLINE | ID: mdl-30688660
Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress-induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A-dependent (LDHA-dependent) metabolic rewiring. Chronic stress-induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress-induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological factors in promoting stem-like properties in breast cancer cells. Thus, the LDHA-lowering agent vitamin C can be a potential approach for combating stress-associated breast cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Psicológico / Células Madre Neoplásicas / Neoplasias de la Mama / Epinefrina / L-Lactato Deshidrogenasa Límite: Animals / Female / Humans Idioma: En Revista: J Clin Invest Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Psicológico / Células Madre Neoplásicas / Neoplasias de la Mama / Epinefrina / L-Lactato Deshidrogenasa Límite: Animals / Female / Humans Idioma: En Revista: J Clin Invest Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos