Metabolic catastrophe as a means to cancer cell death
Open accessAbstract
During tumorigenesis, normal growth mechanisms are deregulated and safeguards that eliminate abnormal cells by apoptosis are disabled. Tumor cells must also increase nutrient uptake and angiogenesis to support the upregulation of metabolism necessary for unrestricted growth. In addition, they have to rely on inefficient energy production by glycolysis. This glycolytic state can result from mutations that promote cell proliferation, the hypoxic tumor microenvironment and perhaps mitochondrial malfunction. Moreover, the very signals that enable unrestricted cell proliferation inhibit autophagy, which normally sustains cells during nutrient limitation. In tumors, inactivation of the autophagy pathway may enhance necrosis and inflammation and promote genomic instability, which can further enhance tumor growth. Thus, tumor cells cannot adapt efficiently to metabolic stress and could be induced to die by metabolic catastrophe, in which high energy demand is contrasted by insufficient energy production. Efforts to exploit this unique metabolic state clinically previously focused mainly on detecting tissue displaying increased glycolytic metabolism. The challenge now is to induce metabolic catastrophe therapeutically as an approach to killing the unkillable cells.
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Autophagy is required for generation of the find-me signal lysophosphatidylcholine and the eat-me signal phosphatidylserine exposure.
“Autophagy has been shown to be required for the generation of the find-me signal lysophosphatidylcholine and the eat-me signal generated by phosphatidylserine exposure 63 (Box 4)”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [63]
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- Authors
- Jin, S., DiPaola, R. S., Mathew, R., & White, E.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Rutgers Cancer Institute (US)
- Corresponding author
- White, Eileen
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2007-02-01
- Volume
- 120
- Issue
- 3
- Pages
- 379-383
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC2857576
- OpenAlex
- W2164300744
- Cited by
- 229
- References
- 46
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 11 · 2019: 8 · 2018: 12 · 2017: 5 · 2016: 8 · 2015: 13 · 2014: 17 · 2013: 11 · 2012: 14
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R37CA053370)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- cancer cell death, cancer metabolism, glycolysis, tumor hypoxia, mitochondrial dysfunction, autophagy inhibition, genomic instability, tumor microenvironment, metabolic stress, cancer therapy
- MeSH terms
- Beclin-1, Animals, Autophagy, Glucose, Glycolysis, Humans, Models, Biological, Necrosis, Neoplasms, Protein Kinases, Proteins, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, Metabolic Networks and Pathways, TOR Serine-Threonine Kinases
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