The Fundamental Role of the p53 Pathway in Tumor Metabolism and Its Implication in Tumor Therapy

Abstract

It is well established that the altered metabolism exhibited by cancer cells, including high rates of glycolysis, lactate production, and biosynthesis of lipids, nucleotides, and other macromolecules, and which may occur either as a consequence or as a cause of tumorigenesis, plays an essential role in cancer progression. Recently, the tumor suppressor p53 was found to play a central role in this process. Here, we review the role of p53 in modulating tumor metabolism. Specifically, we focus on the functions of p53 in regulating aerobic glycolysis, oxidative phosphorylation, the pentose phosphate pathway, fatty acid synthesis and oxidation, and glutamine metabolism, and we discuss the therapeutic strategy whereby p53 helps to prevent malignant progression.

Cell Cycle Regulators Guide Mitochondrial Activity in Radiation-Induced Adaptive Response

“…Additionally, mitochondria affect cell fate by interconnecting glycolysis and the pentose phosphate signaling pathways to cell cycle progression and apoptosis (33,60,113,126,184,189,218). Essential nuclear events are shown to be affected by cellular nutrient metabolism via the regulation of D type cyclins, cyclin-dependent kinases (CDKs), p53, and B-cell lymphoma 2 (Bcl-2) proteins (19,26,43,95,176,190,205,234).…”

Spatial Distribution of Cellular Function: The Partitioning of Proteins between Mitochondria and the Nucleus in MCF7 Breast Cancer Cells

“…32 A variety of nuclear receptors such as the estrogen, PPARγ2, glucocorticoid, and c-ErbAα1 (thyroid hormone) receptors as well as transcription factors such as AP1, CREB, NF-κB, Stat3 and p53 can translocate to mitochondria where they seem to be involved in transcriptional, DNA repair and apoptotic functions. [33][34][35][36] Recently an export system that transfers proteins from mitochondria to peroxisomes via vesicular trafficking has also been identified. 37 These dynamic properties of mitochondria mean that the mitochondrial proteome is not static, but varies with cell type and state.…”

L’effet Warburg

“…En plus de cette fonction de gène suppresseur de tumeur, p53 participe à la régulation du métabolisme [21,43]. En effet, p53 contrôle négativement la glycolyse en activant l'expression de TIGAR (TP53-induced glycolysis regulator), qui réduit le niveau du fructose-2,6-bisphosphate intracellulaire [22].…”