Robust metabolic adaptation underlying tumor progression

Abstract

Tumor metabolism represents the end point of many signal cascades recruited by oncogenic activation. Energy metabolism of cancer cells attracted the attention of biochemists over eight decades ago. For example, high consume of glucose and high lactate production under aerobic conditions make up one of the most fundamental characteristics of cancer cells and has been exploited for diagnosis. At the same time, study of the metabolic status of tumor cells during tumor progression reveals characteristic adaptations during carcinogenesis. Although these metabolic adaptations are not the main defects that cause cancer, they may confer advantages to survive. In this review, we discuss the main metabolic hot spots and their relationship with main tumor progression events. An accurate metabolic map of the many tumor phenotypes could offer new options in the treatment of cancer.Keywords Tumor metabolism Á Warburg effect Á Regulation of glucose metabolism in tumors Á Acidosis and tumor progression Á Biosynthetic pathways in tumoral metabolism Á Alternative to glycolytic energy conversion Á Isoenzyme expression in tumor cells Á Tumor metabolism and apoptosis1 Introduction

Histone deacetylase inhibition results in a common metabolic profile associated with HT29 differentiation

“… 2004 ; Vizán et al . 2008 ). The decrease in lactate enrichment (Σ mn ) and in the glycolytic rate was more prominent after inhibition of histone deacetylases by NaB and TSA due to the suppression of tumor glucose uptake and glycolysis.…”

Identification of biomarkers for apoptosis in cancer cell lines using metabolomics: tools for individualized medicine

“…It can also provide comprehensive insights into intermediate phenotypes (providing ‘snapshots’ of a changing system) not depicted by other omics approaches. The features revealed by metabolomic studies are not only biological end‐points but are considered to be driving forces in the pathophysiology of human diseases .…”

“…Examples of these metabolic processes include amino acid turnover and the tricarboxylic acid cycle , glucose oxidation and the pentose cycle as well as hypoxia‐induced changes . Some of the metabolic features in cancer can be traced to epigenetic events . The general metabolic characteristics observed in cancer are summarized in Table .…”

How close is the bench to the bedside? Metabolic profiling in cancer research

“…Some of these characteristics can be traced back to the reprogramming of cellular bioenergetic pathways. The key pathways that behave differently between tumor and normal cells include the glycolysis and pentose phosphate pathways, nucleotide and protein biosynthesis, lipid and phospholipid turnover, the citric acid cycle and redox stress pathways (Figure 1 ) [ 2 , 3 ]. Essentially all pathways needed for cellular growth and proliferation are affected, and many of these have been targeted for drug research and development [ 2 , 4 ].…”