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Front. Oncol. | doi: 10.3389/fonc.2019.00753

The Flick of a Switch: Conferring Survival Advantage to Breast Cancers Stem Cells Through Metabolic Plasticity

  • 1Department of Pathology, Faculty of Medicine, Dalhousie University, Canada
  • 2Dalhousie University, Canada

Within heterogeneous tumors, cancer stem cell (CSC) populations exhibit the greatest tumor initiation potential, promote metastasis, and contribute to therapy resistance. For breast cancer specifically, CSCs are identified by CD44highCD24low cell surface marker expression and increased aldehyde dehydrogenase activity. In general, bulk breast tumor cells possess altered energetics characterized by aerobic glycolysis. In contrast, breast CSCs appear to have adaptive metabolic plasticity that allows these tumor-initiating cells to switch between glycolysis and oxidative phosphorylation, depending on factors present in the tumor microenvironment (e.g. hypoxia, reactive oxygen species, availability of glucose). In this article, we review the regulatory molecules that may facilitate the metabolic plasticity of breast CSCs. These regulatory factors include epigenetic chromatin modifiers, non-coding RNAs, transcriptional repressors, transcription factors, energy and stress sensors, and metabolic enzymes. Furthermore, breast cancer cells acquire CSC-like characteristics and altered energetics by undergoing epithelial-mesenchymal transition (EMT). This energy costly process is paired with reprogrammed glucose metabolism by epigenetic modifiers that regulate expression of both EMT and other metabolism-regulating genes. The survival advantage imparted to breast CSCs by metabolic plasticity suggests that targeting the factors that mediate the energetic switch should hinder tumorigenesis and lead to improved patient outcomes.

Keywords: Breast cancer stem cells, Glycolysis, Oxidative Phosphorylation, metabolic plasticity, lncRNA

Received: 09 Jun 2019; Accepted: 26 Jul 2019.

Edited by:

Dayanidhi Raman, College of Medicine and Life Sciences, University of Toledo, United States

Reviewed by:

Ada Pesapane, Department of Clinical Medicine and Surgery, School of Medicine and Surgery, University of Naples Federico II, Italy
Masahiko Tanabe, The University of Tokyo, Japan  

Copyright: © 2019 Walsh, Cruickshank, Brown and Marcato. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Paola Marcato, Dalhousie University, Halifax, B3H 4R2, Nova Scotia, Canada, paola.marcato@dal.ca