The unfolded protein response and cancer: A brighter future unfolding?
Abstract
Mammalian cells are bathed in an interstitial fluid that has a tightly regulated composition in healthy states. Interstitial fluid provides cells with all the necessary metabolic substrates (oxygen, glucose, amino acids, etc.), and waste molecules are removed by diffusion gradients that are controlled by local vascular perfusion. The health and normal function of all cells within a body is dependent on the maintenance of this microenvironment. However, many disease states cause fluctuations in this, and in some instances, these might be of sufficient severity to stress and/or be toxic to the cell. Cells have developed a number of responses to enable their survival in a hostile environment. This article discusses one such pathway--the unfolded protein response and its relationship to cancer. The molecular signalling cascade, the mechanism of its activation in cancer and the consequences of its activation for a tumour are discussed, as are clinical studies and potential translational approaches for utilising this pathway for tumour targeting.
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The UPR is often activated in many cancers due to abnormal microcirculation and high glucose needs of tumours, resulting in metabolic stress.
“The UPR is often activated in many cancers [27] due to their abnormal microcirculation (which leads to cellular hypoxia and acidosis) and the high glucose needs of tumours (Warberg effect), resulting in metabolic stress.”
From Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies (2020) · cites this paper as [27]
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ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
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Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies
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“The UPR is often activated in many cancers [27] due to their abnormal microcirculation (which leads to cellular hypoxia and acidosis) and the high glucose needs of tumours (Warberg effect), resulting in metabolic stress.”
BackgroundSelf-citation
- Authors
- Scriven, P., Brown, N. J., Pockley, A. G., & Wyld, L.
- Affiliations
- Royal Hallamshire Hospital (GB)
- Corresponding author
- Scriven, Peter
- Venue
- Journal of Molecular Medicine
- Published
- 2007-01-10
- Volume
- 85
- Issue
- 4
- Pages
- 331-341
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- OpenAlex
- W2101203508
- Cited by
- 67
- References
- 139
- Citations by year
- 2026: 1 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 2 · 2013: 4 · 2012: 5
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- unfolded protein response, cancer, tumor microenvironment, interstitial fluid, endoplasmic reticulum stress, tumor targeting, translational cancer therapy
- MeSH terms
- Animals, Endoplasmic Reticulum, Humans, Neoplasm Proteins, Neoplasms, Protein Processing, Post-Translational, Signal Transduction, Apoptosis, Protein Folding
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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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