Abstract
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 CD44high CD24low 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.
Original language | English |
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Article number | 753 |
Journal | Frontiers in Oncology |
Volume | 9 |
Issue number | AUG |
DOIs | |
Publication status | Published - 2019 |
Bibliographical note
Funding Information:Support was provided by grant funding to PM from the Canadian Institutes of Health Research (CIHR, PJT 162313). BC was supported by Killam Laureate and Nova Scotia Research and Innovation Graduate Scholarships. JB was supported by a scholarship from the Beatrice Hunter Cancer Research Institute and the Terry Fox Research Institute.
Publisher Copyright:
© 2019 Walsh, Cruickshank, Brown and Marcato.
ASJC Scopus Subject Areas
- Oncology
- Cancer Research