Abstract
A central characteristic of many types of cancer is altered energy metabolism processes such as enhanced glucose uptake and glycolysis and decreased oxidative metabolism. The regulation of energy metabolism is an elaborate process involving regulatory proteins such as HIF (pro-metastatic protein), which reduces oxidative metabolism, and some other proteins such as tumour suppressors that promote oxidative phosphorylation. In recent years, it has been demonstrated that signal transducer and activator of transcription (STAT) proteins play a pivotal role in metabolism regulation. STAT3 and STAT5 are essential regulators of cytokine- or growth factor-induced cell survival and proliferation, as well as the crosstalk between STAT signalling and oxidative metabolism. Several reports suggest that the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of hypoxia-inducible factors and therefore, the alteration of mitochondrial activity. It seems that STAT proteins function as an integrative centre for different growth and survival signals for energy and respiratory metabolism. This review summarises the functions of STAT3 and STAT5 in the regulation of some metabolism-related genes and the importance of oxygen in the tumour microenvironment to regulate cell metabolism, particularly in the metabolic pathways that are involved in energy production in cancer cells.
Highlights
All cells need energy and for this purpose, they use macromolecules, which are degraded and cells obtain the necessary energy for their essential functions
The mitochondrial localisation of STAT5 suggests that it may be involved in mitochondrial gene regulation, coinciding with the metabolic shift to aerobic glycolysis observed in T cells and leukaemias stimulated with cytokines
Glucose uptake is enhanced in haemopoietic stem cells (HSC) cells expressing STAT5, and in these cells, Hypoxia-inducible factor (HIF)-2α is required for the upregulation of genes associated with glucose metabolism
Summary
All cells need energy and for this purpose, they use macromolecules, which are degraded and cells obtain the necessary energy for their essential functions. Glucose is the primary fuel and oxidises, via glycolysis, to provide energy for all cells (Figure 1) This metabolic pathway consists of 10 consecutive enzymatic reactions that convert glucose into two molecules of pyruvate, which connect with other metabolic pathways. The functions of glycolysis are in the generation of high energy molecules (ATP and NADH) as a source of cellular energy for aerobic respiration (in the presence of oxygen) and fermentation Thisrate pathway is critical for cancer It cells it generates pentose support a high of nucleic acid synthesis. The TCA cycle is composed of a series of enzymatic reactions occurring occurring in the mitochondrial matrix and issource a vitalofsource of metabolic intermediates, providing in the mitochondrial matrix and is a vital metabolic intermediates, providing energy, macromolecules, and redox balance to the cell This is important for highly proliferating cells, like energy,2019, macromolecules, Cancers.
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