Caveolin-1 inhibits breast cancer stem cells via c-Myc-mediated metabolic reprogramming

Shengqi Wang, Neng Wang, Yifeng Zheng, Bowen Yang, Pengxi Liu, Fengxue Zhang, Min LI, Juxian Song, Xu Chang, Zhiyu Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number450
JournalCell Death and Disease
Volume11
Issue number6
DOIs
Publication statusPublished - 1 Jun 2020

Scopus Subject Areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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