Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A and Promotes Breast Cancer Stem-Like Cells

Authors

Bai Cui, Dalian Medical University, China
Yuanyuan Luo, Dalian Medical University, China
Pengfei Tian, Dalian Medical University, China
Fei Peng, Dalian Medical University, China
Jinxin Lu, Dalian Medical University, China
Yongliang Yang, Dalian University of Technology, China
Qitong Su, Dalian Medical University, China
Bing Liu, Dalian Medical University, China
Jiachuan Yu, Dalian Medical University, China
Xi Luo, Dalian Medical University, China
Liu Yin, Dalian Medical University, China
Wei Cheng, Dalian Medical University, China
Fan An, Dalian Medical University, China
Bin He, Sun Yat-sen University, China
Dapeng Liang, Dalian Medical University, China
Sijin Wu, Dalian University of Technology, China
Peng Chu, Dalian Medical University, China
Luyao Song, Dalian Medical University, China
Xinyu Liu, Chinese Academy of Sciences, China
Huandong Luo, Dalian Medical University, China
Binhua P. Zhou, University of KentuckyFollow

Abstract

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.

Document Type

Article

Publication Date

3-2019

Notes/Citation Information

Published in The Journal of Clinical Investigation, v. 129, no. 3.

This work is licensed under the Creative Commons Attribution 4.0 International License.

The first 20 authors and the author from the University of Kentucky are shown on the author list above. Please refer to the downloaded document for the complete author list.

Digital Object Identifier (DOI)

https://doi.org/10.1172/jci121685

Funding Information

This research work was supported by the National Natural Science Foundation of China (81820108024 to QL;81630005 to QL; 81573025 to QL; and 81703091 to FA); the Science and Technology Planning Project of Guangzhou (201604020163 to QL); and the Dalian High-level Talent Innovation Program (2016RD12 to QL). EWFL’s work is supported by the Medical Research Council (MRC) (MR/N012097/1); Cancer Research UK (CRUK) (C37/A12011; C37/A18784); Breast Cancer Now (2012MayPR070; 2012NovPhD016); the CRUK Imperial Centre, Imperial Experimental Cancer Medicine Centre (ECMC); and the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC).

Repository Citation

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; and Zhou, Binhua P., "Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A and Promotes Breast Cancer Stem-Like Cells" (2019). Molecular and Cellular Biochemistry Faculty Publications. 190.
https://uknowledge.uky.edu/biochem_facpub/190