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Theor Biol Med Model. 2013 Jun 10;10:39. doi: 10.1186/1742-4682-10-39.

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

Author information

1
Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, Boston, MA 02142, USA. edward.rietman@tufts.edu

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.

PMID:
23758735
PMCID:
PMC3689044
DOI:
10.1186/1742-4682-10-39
[Indexed for MEDLINE]
Free PMC Article
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