TY - JOUR
T1 - Caveolin-1 inhibits breast cancer stem cells via c-Myc-mediated metabolic reprogramming
AU - Wang, Shengqi
AU - Wang, Neng
AU - Zheng, Yifeng
AU - Yang, Bowen
AU - Liu, Pengxi
AU - Zhang, Fengxue
AU - Li, Min
AU - Song, Juxian
AU - Chang, Xu
AU - Wang, Zhiyu
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (81703749, 81703764, 81973526, and 81873306), Guangdong Science and Technology Department (2016A030306025), Guangdong High-level Personnel of Special Support Program (A1-3002-16-111-003), Department of Education of Guangdong Province (2018KZDXM022 and A1-2606-19-111-009), Guangdong traditional Chinese medicine bureau project (20181132, 20182044, 20201132), the Ph.D. Start-up Fund of Natural Science Foundation of Guangdong Province (2017A030310213 and 2018A030310506), Science and Technology Planning Project of Guangdong Province (2017B030314166), Guangzhou science and technology project (201904010407), Medical and Health program of Panyu Science & Technology Plan (2019-Z04-05), the Specific Research Fund for TCM Science and Technology of Guangdong provincial Hospital of Chinese Medicine (YN2018MJ07, YN2018QJ08), and the Foundation for Young Scholars of Guangzhou University of Chinese Medicine (QNYC20190101).
Publisher Copyright:
© The Author(s) 2020
PY - 2020/6/11
Y1 - 2020/6/11
N2 - Breast cancer stem cells (BCSCs) are considered to be the root of breast cancer occurrence and progression. However, the characteristics and regulatory mechanisms of BCSCs metabolism have been poorly revealed, which hinders the development of metabolism-targeted treatment strategies for BCSCs elimination. Herein, we demonstrated that the downregulation of Caveolin-1 (Cav-1) usually occurred in BCSCs and was associated with a metabolic switch from mitochondrial respiration to aerobic glycolysis. Meanwhile, Cav-1 could inhibit the self-renewal capacity and aerobic glycolysis activity of BCSCs. Furthermore, Cav-1 loss was associated with accelerated mammary-ductal hyperplasia and mammary-tumor formation in transgenic mice, which was accompanied by enrichment and enhanced aerobic glycolysis activity of BCSCs. Mechanistically, Cav-1 could promote Von Hippel-Lindau (VHL)-mediated ubiquitination and degradation of c-Myc in BCSCs through the proteasome pathway. Notably, epithelial Cav-1 expression significantly correlated with a better overall survival and delayed onset age of breast cancer patients. Together, our work uncovers the characteristics and regulatory mechanisms of BCSCs metabolism and highlights Cav-1-targeted treatments as a promising strategy for BCSCs elimination.
AB - Breast cancer stem cells (BCSCs) are considered to be the root of breast cancer occurrence and progression. However, the characteristics and regulatory mechanisms of BCSCs metabolism have been poorly revealed, which hinders the development of metabolism-targeted treatment strategies for BCSCs elimination. Herein, we demonstrated that the downregulation of Caveolin-1 (Cav-1) usually occurred in BCSCs and was associated with a metabolic switch from mitochondrial respiration to aerobic glycolysis. Meanwhile, Cav-1 could inhibit the self-renewal capacity and aerobic glycolysis activity of BCSCs. Furthermore, Cav-1 loss was associated with accelerated mammary-ductal hyperplasia and mammary-tumor formation in transgenic mice, which was accompanied by enrichment and enhanced aerobic glycolysis activity of BCSCs. Mechanistically, Cav-1 could promote Von Hippel-Lindau (VHL)-mediated ubiquitination and degradation of c-Myc in BCSCs through the proteasome pathway. Notably, epithelial Cav-1 expression significantly correlated with a better overall survival and delayed onset age of breast cancer patients. Together, our work uncovers the characteristics and regulatory mechanisms of BCSCs metabolism and highlights Cav-1-targeted treatments as a promising strategy for BCSCs elimination.
UR - http://www.scopus.com/inward/record.url?scp=85086370017&partnerID=8YFLogxK
U2 - 10.1038/s41419-020-2667-x
DO - 10.1038/s41419-020-2667-x
M3 - Journal article
C2 - 32528105
AN - SCOPUS:85086370017
SN - 2041-4889
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 6
M1 - 450
ER -
