An integrated multidisciplinary model describing initiation of cancer and the Warburg hypothesis

Abstract

Background: In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis, whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells. We show that this may result in cancer via mitotic failure, recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer, to a biophysical defect that may contribute to cancer initiation. Model. Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance, disrupted microtubule dynamics, and finally, genomic instability, from which cancers can arise. Specifically, we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer. Conclusions: A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell. Contrary to current understanding, this effect may precipitate cancer development, rather than follow from it, providing new insights into carcinogenesis, cancer treatment, and prevention. © 2013 Rietman et al.; licensee BioMed Central Ltd.