Energy oversupply to tissues: A single mechanism possibly underlying multiple cancer risk factors

Daniel J. Wu, C Athena Aktipis, John W. Pepper

Research output: Contribution to journalArticle

Abstract

Background and objectives: Several major risk factors for cancer involve vascular oversupply of energy to affected tissues. These include obesity, diabetes and chronic inflammation. Here, we propose a potential mechanistic explanation for the association between energy oversupply and cancer risk, which we call the metabolic cancer suppression hypothesis: We hypothesize that oncogenesis is normally suppressed by organismal physiology that regulates and strictly limits normal energy supply to somatic cells, and that this protection is removed by abnormal oversupply of energy. Methodology: We evaluate this hypothesis using a computational model of somatic cell evolution to simulate experimental manipulation of the vascular energy supply to a tissue. The model simulates the evolutionary dynamics of somatic cells during oncogenesis. Results: In our simulation experiment, we found that under plausible biological assumptions, elevated energy supply to a tissue led to the evolution of elevated energy uptake by somatic cells, leading to the rapid evolution of both defining traits of cancer cells: Hyperproliferation, and tissue invasion. Conclusions and implications: Our results support the hypothesis of metabolic cancer suppression, suggesting that vascular oversupply of energetic resources to somatic cells removes normal energetic limitations on cell proliferation, and that this accelerates cellular evolution toward cancer. Various predictions of this hypothesis are amenable to empirical testing, and have promising implications for translational research toward clinical cancer prevention.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalEvolution, Medicine and Public Health
Volume2019
Issue number1
DOIs
StatePublished - Jan 21 2019

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risk factor
cancer
risk factors
somatic cells
neoplasms
energy
Neoplasms
blood vessels
Blood Vessels
carcinogenesis
energetics
Carcinogenesis
Clonal Evolution
obesity
diabetes
Translational Medical Research
Cytoprotection
physiology
tissues
cancer risk

Keywords

  • cancer prevention
  • cancercell metabolismcell energeticsoncogenesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Ecology, Evolution, Behavior and Systematics
  • Health, Toxicology and Mutagenesis

Cite this

Energy oversupply to tissues : A single mechanism possibly underlying multiple cancer risk factors. / Wu, Daniel J.; Aktipis, C Athena; Pepper, John W.

In: Evolution, Medicine and Public Health, Vol. 2019, No. 1, 21.01.2019, p. 9-16.

Research output: Contribution to journalArticle

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abstract = "Background and objectives: Several major risk factors for cancer involve vascular oversupply of energy to affected tissues. These include obesity, diabetes and chronic inflammation. Here, we propose a potential mechanistic explanation for the association between energy oversupply and cancer risk, which we call the metabolic cancer suppression hypothesis: We hypothesize that oncogenesis is normally suppressed by organismal physiology that regulates and strictly limits normal energy supply to somatic cells, and that this protection is removed by abnormal oversupply of energy. Methodology: We evaluate this hypothesis using a computational model of somatic cell evolution to simulate experimental manipulation of the vascular energy supply to a tissue. The model simulates the evolutionary dynamics of somatic cells during oncogenesis. Results: In our simulation experiment, we found that under plausible biological assumptions, elevated energy supply to a tissue led to the evolution of elevated energy uptake by somatic cells, leading to the rapid evolution of both defining traits of cancer cells: Hyperproliferation, and tissue invasion. Conclusions and implications: Our results support the hypothesis of metabolic cancer suppression, suggesting that vascular oversupply of energetic resources to somatic cells removes normal energetic limitations on cell proliferation, and that this accelerates cellular evolution toward cancer. Various predictions of this hypothesis are amenable to empirical testing, and have promising implications for translational research toward clinical cancer prevention.",
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