Abstract
Cancer cells characteristically have a high proliferation rate. Because tumor growth depends on energy-consuming anabolic processes, including biosynthesis of protein, lipid, and nucleotides, many tumor-associated conditions, including intermittent oxygen deficiency due to insufficient vascularization, oxidative stress, and nutrient deprivation, results from fast growth. To cope with these environmental stressors, cancer cells, including cancer stem cells, must adapt their metabolism to maintain cellular homeostasis. It is well- known that cancer stem cells (CSC) reprogram their metabolism to adapt to live in hypoxic niches. They usually change from oxidative phosphorylation to increased aerobic glycolysis even in the presence of oxygen. However, as opposed to most differentiated cancer cells relying on glycolysis, CSCs can be highly glycolytic or oxidative phosphorylation-dependent, displaying high metabolic plasticity. Although the influence of the metabolic and nutrient-sensing pathways on the maintenance of stemness has been recognized, the molecular mechanisms that link these pathways to stemness are not well known. Here in this review, we describe the most relevant signaling pathways involved in nutrient sensing and cancer cell survival. Among them, Adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway, mTOR pathway, and Hexosamine Biosynthetic Pathway (HBP) are critical sensors of cellular energy and nutrient status in cancer cells and interact in complex and dynamic ways.
Highlights
Tumors are not uniform but rather heterogeneous in function
Using nutrient-sensing pathways such as those regulated by Hexosamine Biosynthetic Pathway (HBP), mammalian target of rapamycin (mTOR), and AMPK, stem cells respond to nutritional cues, and the crosstalk between them is key to maintaining stemness (Figure 6)
Accumulating experimental evidence has shown that cancer-related glucose metabolism dysregulations interact with increased glucose flux via HBP, leading to high O-GlcNAc transferase (OGT) expression and global levels of OGlcNAcylation
Summary
The involvement of stem cell cancer (CSC) subpopulations has been demonstrated in almost all human cancers These cells have the capacity to replicate the entire tumor and are often denoted as tumor-initiating cells (TICs). They drive tumor formation, metastatic spread, and relapse, making them a daunting yet promising goal to eliminate cancer [1]. Cancer cells reprogram their metabolic procedures to meet their needs, such as their high proliferation rate: they induce rapid ATP generation to maintain energy status, increase the biosynthesis of macromolecules and induce strict regulation of the cellular redox status
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