Cited by 486Metabolism, Diabetes, and CancerCancer, Hypoxia, and MetabolismPI3K/AKT/mTOR signaling in cancer

Cellular Metabolic Stress: Considering How Cells Respond to Nutrient Excess

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Wellen, Kathryn E., Thompson, Craig B.·2010·Molecular Cell

Abstract

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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Crossref · 10.1016/j.molcel.2010.10.004

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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).”
  • 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)
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
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

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