Metabolic profile of the Warburg effect as a tool for molecular prognosis and diagnosis of cancer

ABSTRACT

Introduction

Adaptations of eukaryotic cells to environmental changes are important for their survival. However, under some circumstances, microenvironmental changes promote that eukaryotic cells utilize a metabolic signature resembling a unicellular organism named the Warburg effect. Most cancer cells share the Warburg effect displaying lactic fermentation and high glucose uptake. The Warburg effect also induces a metabolic rewiring stimulating glutamine consumption and lipid synthesis, also considered cancer hallmarks. Amino acid metabolism alteration due to the Warburg effect increases plasma levels of proline and branched-chain amino acids in several cancer types. Proline and lipids are probably used as electron transfer molecules in carcinogenic cells. In addition, branched-chain amino acids fuel the Krebs cycle, protein synthesis, and signaling in cancer cells.

Areas covered

This review covers how metabolomics studies describe changes in some metabolites and proteins associated with the Warburg effect and related metabolic pathways.

Expert opinion

In this review, we analyze the metabolic signature of the Warburg effect and related phenotypes and propose some Warburg effect-related metabolites and proteins (lactate, glucose uptake, glucose transporters, glutamine, branched-chain amino acids, proline, and some lipogenic enzymes) as promising cancer biomarkers.

KEYWORDS:

• Biomarker
• cancer
• diagnosis
• metabolism
• molecular prognosis
• Warburg effect

Article highlights

- The Warburg effect rewires lipid and amino acid metabolisms.

- Warburg effect-derived metabolites and proteins are promising cancer biomarkers.

- High-glucose uptake in cancer cells is a response to lessening in ATP/glucose yield occasioned by the switching from oxidative phosphorylation to substrate-level phosphorylation as the main ATP producing pathway.

- Glutamine fuels the Krebs cycle and serves as a redox donor during the Warburg effect.

- Lipids and proline are synthesized in cancer cells as electrons bins.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.