Conflicting metabolic alterations in cancer stem cells and regulation by the stromal niche

Tadahito Yasuda; Takatsugu Ishimoto; Hideo Baba

doi:10.1016/j.reth.2021.01.005

Conflicting metabolic alterations in cancer stem cells and regulation by the stromal niche

Regen Ther. 2021 Jan 29:17:8-12. doi: 10.1016/j.reth.2021.01.005. eCollection 2021 Jun.

Authors

Tadahito Yasuda^{1

2}, Takatsugu Ishimoto^{1

2}, Hideo Baba^{1

3}

Affiliations

¹ Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
² Gastrointestinal Cancer Biology, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.
³ Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

Recent studies have revealed that cancer stem cells (CSCs) undergo metabolic alterations that differentiate them from non-CSCs. Inhibition of specific metabolic pathways in CSCs has been conducted to eliminate the CSC population in many types of cancer. However, there is conflicting evidence about whether CSCs depend on glycolysis or mitochondrial oxidative phosphorylation (OXPHOS) to maintain their stem cell properties. This review summarizes the latest knowledge regarding CSC-specific metabolic alterations and offers recent evidence that the surrounding microenvironments may play an important role in the maintenance of CSC properties.

Keywords: ALDH, aldehyde dehydrogenase; ATP, adenosine triphosphate; CD44v, CD44 variant isoform; CSCs; CSCs, cancer stem cells; EMT, epithelial–mesenchymal transition; EVs, extracellular vesicles; FAO, fatty acid oxidation; FBP1, fructose-1,6-biphosphatase 1; GLUT1, glucose transporter 1; GP6, glucose-6-phosphate; Glycolysis; HCC, hepatocellular carcinoma; HIF1a, hypoxia inducible factor 1a; IMP2, insulin-like growth factor 2; IncRNAs, long noncoding RNAs; LSCs, leukemia stem cells; Mitochondrial OXPHOS; NRF2, nuclear factor erythroid 2–related factor 2; OXPHOS, oxidative phosphorylation; PDK1, pyruvate dehydrogenase kinase 1; PPP, pentose phosphate pathway; ROS; ROS, reactive oxygen species; SOD2, superoxide dismutase 2; Stromal niche; TCA, tricarboxylic acid; TICs, tumor initiating stem-like cells; mTORC1, mammalian target of rapamycin complex 1.