Journal article
Is cancer a metabolic rebellion against host aging?: In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism
Cell cycle (Georgetown, Tex.), v 11(2)
15 Jan 2012
PMID: 22234241
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aging drives large systemic reductions in oxidative mitochondrial function, shifting the entire body metabolically toward aerobic glycolysis, a.k.a, the Warburg effect. Aging is also one of the most significant risk factors for the development of human cancers, including breast tumors. How are these two findings connected? One simplistic idea is that cancer cells rebel against the aging process by increasing their capacity for oxidative mitochondrial metabolism (OXPHOS). Then, local and systemic aerobic glycolysis in the aging host would provide energy-rich mitochondrial fuels (such as L-lactate and ketones) to directly “fuel” tumor cell growth and metastasis. This would establish a type of parasite-host relationship or “two-compartment tumor metabolism,” with glycolytic/oxidative metabolic coupling. The cancer cells (“the seeds”) would flourish in this nutrient-rich microenvironment (“the soil”), which has been fertilized by host aging. In this scenario, cancer cells are only trying to save themselves from the consequences of aging by engineering a metabolic mutiny, through the amplification of mitochondrial metabolism. We discuss the recent findings of Drs. Ron DePinho (MD Anderson) and Craig Thomspson (Sloan-Kettering) that are also consistent with this new hypothesis, linking cancer progression with metabolic aging. Using data mining and bioinformatics approaches, we also provide key evidence of a role for PGC1a/NRF1 signaling in the pathogenesis of (1) two-compartment tumor metabolism and (2) mitochondrial biogenesis in human breast cancer cells.
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Details
- Title
- Is cancer a metabolic rebellion against host aging?
- Creators
- Adam Ertel - Thomas Jefferson UniversityAristotelis Tsirigos - Computational Genomics Group; IBM Thomas J. Watson Research Center; Yorktown Heights, NY USADiana Whitaker-Menezes - The Jefferson Stem Cell Biology and Regenerative Medicine Center, Philadelphia, PA, USA.Ruth C Birbe - Thomas Jefferson UniversityStephanos Pavlides - The Jefferson Stem Cell Biology and Regenerative Medicine Center, Philadelphia, PA, USA.Ubaldo E Martinez-Outschoorn - The Jefferson Stem Cell Biology and Regenerative Medicine Center, Philadelphia, PA, USA.Richard G Pestell - The Jefferson Stem Cell Biology and Regenerative Medicine Center, Philadelphia, PA, USA.Anthony Howell - Manchester Breast Centre & Breakthrough Breast Cancer Research Unit; Paterson Institute for Cancer Research; Manchester UKFederica Sotgia - The Jefferson Stem Cell Biology and Regenerative Medicine Center, Philadelphia, PA, USA.Michael P Lisanti - The Jefferson Stem Cell Biology and Regenerative Medicine Center, Philadelphia, PA, USA.
- Publication Details
- Cell cycle (Georgetown, Tex.), v 11(2)
- Publisher
- Landes Bioscience
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000299164200017
- Scopus ID
- 2-s2.0-84856100695
- Other Identifier
- 991019176801504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology