Glutamine Metabolism in Cancer Stem Cells: A Complex Liaison in the Tumor Microenvironment

Author:

Pacifico Francesco1ORCID,Leonardi Antonio2ORCID,Crescenzi Elvira1ORCID

Affiliation:

1. Istituto per l’Endocrinologia e l’Oncologia Sperimentale, CNR, Via S. Pansini 5, 80131 Naples, Italy

2. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples “Federico II”, Via S. Pansini 5, 80131 Naples, Italy

Abstract

In this review we focus on the role of glutamine in control of cancer stem cell (CSC) fate. We first provide an overview of glutamine metabolism, and then summarize relevant studies investigating how glutamine metabolism modulates the CSC compartment, concentrating on solid tumors. We schematically describe how glutamine in CSC contributes to several metabolic pathways, such as redox metabolic pathways, ATP production, non-essential aminoacids and nucleotides biosynthesis, and ammonia production. Furthermore, we show that glutamine metabolism is a key regulator of epigenetic modifications in CSC. Finally, we briefly discuss how cancer-associated fibroblasts, adipocytes, and senescent cells in the tumor microenvironment may indirectly influence CSC fate by modulating glutamine availability. We aim to highlight the complexity of glutamine’s role in CSC, which supports our knowledge about metabolic heterogeneity within the CSC population.

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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