Metabolic Plasticity of Cancer Stem Cells in Response to Microenvironmental Cues

SIMPLE SUMMARY: Accumulating evidence indicates the existence of cancer stem cells (CSCs) sub-populations which fuel cancer growth and maintain stemness in different cancers. In addition to the genetic and phenotypic variabilities that differentiate CSCs from non-CSCs counterparts, CSCs adopt a flexible metabolic strategy to sustain their oncogenic and stemness properties, in order to survive and propagate in a hostile tumor microenvironment (TME). TME factors and metabolites exert context-dependent influence on cancer stemness. In addition, the metabolic landscape in TME is complicated by the crosstalk between CSCs and tumor-infiltrating cells. In this review, we will summarize the metabolic interaction between CSCs and various microenvironmental factors and review how this interplay regulates cancer stemness and tumorigenesis. ABSTRACT: An increasing body of evidence suggests that cancer stem cells (CSCs) utilize reprogrammed metabolic strategies to adapt to a hostile tumor microenvironment (TME) for survival and stemness maintenance. Such a metabolic alteration in CSCs is facilitated by microenvironmental cues including metabolites such as glucose, amino acids and lipids, and environmental properties such as hypoxic and acidic TME. Similarly, metabolites uptake from the diet exerts critical imprints to the metabolism profile of CSCs and directly influence the maintenance of the CSC population. Moreover, CSCs interact with tumor-infiltrating cells inside the CSC niche to promote cancer stemness, ultimately contributing to tumor development and progression. Understanding the underlying mechanisms of how CSCs employ metabolic plasticity in response to different microenvironmental cues represents a therapeutic opportunity for better cancer treatment.