Cellular Metabolic Stress: Considering How Cells Respond to Nutrient Excess
Open accessAbstract
Nutrient stress is generally considered from the standpoint of how cells detect and respond to an insufficient supply of nutrients to meet their bioenergetic needs. However, cells also experience stress as a result of nutrient excess, during which reactive oxygen species (ROS) production exceeds that required for normal physiological responses. This may occur as a result of oncogene activation or chronic exposure to growth factors combined with high levels of nutrients. As a result, multiple mechanisms have evolved to allow cells to detect and adapt to elevated levels of intracellular metabolites, including promotion of signaling and proliferation by ROS, amino acid-dependent mTOR activation, and regulation of signaling and transcription through metabolite-sensitive protein modifications. We discuss how each of these responses can contribute to the development and/or progression of cancer under conditions of cellular nutrient excess and their potential roles in linking chronic organismal over-nutrition (obesity) with cancer.
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Obesity induced by HF diet leads to enhanced oxidative stress in rodents.
“Thus, obesity induced by an HF diet leads to enhanced oxidative stress in rodents (3, 46).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [46]
The same signaling cascades activated in classical inflammation can be stimulated by cytokines arising from metabolically active tissues in response to excess nutrients.
“The basis for this reappraisal is the recognition that the same signaling cascades that are activated in classical inflammation in response to pathogens, including activator protein 1 (AP1), NF-κ B and interferon regulatory factors (IRFs), can be stimulated by cytokines arising from a variety of metabolically active tissues, such as adipose tissue, muscle and liver, and their resident immune cells”
From Placental Origins of Chronic Disease (2016) · cites this paper as [567]
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- Authors
- Wellen, K. E., & Thompson, C. B.
- Affiliations
- Abramson Cancer Center (US)
- Corresponding author
- Thompson, Craig B.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 40
- Issue
- 2
- Pages
- 323-332
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3190402
- OpenAlex
- W2066963700
- Cited by
- 486
- References
- 109
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 17 · 2023: 32 · 2022: 33 · 2021: 42 · 2020: 38 · 2019: 34 · 2018: 40 · 2017: 26 · 2016: 25 · 2015: 21 · 2014: 42 · 2013: 32 · 2012: 36
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- National Cancer Institute (R01CA092660, R01CA105463, R01CA099179)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- nutrient excess, reactive oxygen species, oncogene activation, mTOR signaling, amino acids, tumor progression, obesity, overnutrition, growth factor signaling, cell proliferation
- MeSH terms
- Animals, Cell Physiological Phenomena, Energy Metabolism, Humans, Models, Biological, Neoplasms, Stress, Physiological, Signal Transduction, Reactive Oxygen Species, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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