A 'fault' in the cellular power plant explains the abnormal metabolism of tumours

The German Nobel laureate Otto Warburg, one of twentieth century's leading scientists observed that tumour cells exhibit an increased aerobic glucose metabolism in their glycolysis process.

Seeing that, Warburg concluded that cancer should be interpreted as a mitochondrial dysfunction, but his hypothesis was not accepted at the time, and was forgotten by the scientific community until it was recently experimentally confirmed, arousing great interest in biotechnological and pharmaceutical companies.

The comeback of Warburg's hypothesis has been greatly helped by the research of a group of Spanish physicians and scientists from the “12 de octubre” hospital in Madrid (López-Ríos, García-García, Pozo-Rodriguez, López-Encuentra and Ballestín) and from the “Universidad Autónoma de Madrid” (Sanchéz-Aragó, Ortega y Berrendero) under the direction of José Manuel Cuezva, professor of biochemistry and molecular biology at the “Centro de Biología Molecular Severo Ochoa”.

Their latest research work, recently published in the prestigious journal Cancer Research, describes how the activity or expression of the protein beta-F1-ATPase (responsible for the synthesis of ATP) that controls the aerobic usage of glucose in a cell, shows an inverse correlation between the glycolysis process and the metabolic energy supply of mitochondria.

The study carried out by Dr. Cuezva´s team focused on lung cancer patients. The increase in glucose capture by the tumours was measured using Positron emission tomography (PET), and then contrasted with the expression of protein beta-F1-ATPase, determined from the tumours obtained after surgery, finding an inverse correlation between the two variables.

They also describe in their research work, that when the beta-F1-ATPase protein expression is inhibited or its activity reduced in the carcinomas, the tumour cells are forced to increase their intake of glucose by glycolytic means. Although this research trend is not new, since this same team already has reported in earlier work how the disruption of the mitochondrial bioenergetic function is a metabolic signature of tumours, and how this could be used in clinical prognosis of patients with colorectal, lung or breast cancer. Among other applications that the team and other research groups consider promising are the uses of this signature as a tool to predict the reaction of a patient to a treatment, or as a therapeutic target against cancer.

The commercial applications of such prospective therapies are already protected by a patent that is owned by the “Universidad Autónoma de Madrid” and is licensed to the Spanish biotechnology firm “Fina Biotech, S.L”. Therefore this study might not sound like a new scientific discovery, but it provides the first evidence that integrates molecular and functional data supporting Warburg's hypothesis emphasizing the importance of the mitochondria in human pathology and more specifically in cancer biology.