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Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem-like cells

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Title: Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem-like cells
Authors: Lam, E
Item Type: Journal Article
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.
Issue Date: 1-Mar-2019
Date of Acceptance: 30-Nov-2018
URI: http://hdl.handle.net/10044/1/66577
DOI: https://dx.doi.org/10.1172/JCI121685
ISSN: 0021-9738
Publisher: American Society for Clinical Investigation
Start Page: 1030
End Page: 1046
Journal / Book Title: Journal of Clinical Investigation
Volume: 129
Issue: 3
Copyright Statement: © 2019 Cui et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Breast Cancer Now
Breast Cancer Now
Medical Research Council (MRC)
Cancer Research UK
Funder's Grant Number: 2012NovemberPhD016
2012MayPR070
MR/N012097/1
C37/A12011
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
SUPPRESSES TUMOR-GROWTH
THERAPEUTIC TARGET
HEMATOPOIETIC STEM
PROTEIN-KINASE
LACTIC-ACID
C-MYC
GLYCOLYSIS
METASTASIS
INVASION
OXAMATE
Breast cancer
Metabolism
Oncology
Immunology
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2019-01-28
Appears in Collections:Department of Surgery and Cancer