The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
The metabolism of proline, a stress substrate, modulates carcinogenic pathways
Open accessAbstract
The resurgence of interest in tumor metabolism has led investigators to emphasize the metabolism of proline as a "stress substrate" and to suggest this pathway as a potential anti-tumor target. Proline oxidase, a.k.a. proline dehydrogenase (POX/PRODH), catalyzes the first step in proline degradation and uses proline to generate ATP for survival or reactive oxygen species for programmed cell death. POX/PRODH is induced by p53 under genotoxic stress and initiates apoptosis by both mitochondrial and death receptor pathways. Furthermore, POX/PRODH is induced by PPARgamma and its pharmacologic ligands, the thiazolidinediones. The anti-tumor effects of PPARgamma may be critically dependent on POX/PRODH. In addition, it is upregulated by nutrient stress through the mTOR pathway to maintain ATP levels. We propose that proline is made available as a stress substrate by the degradation of collagen in the microenvironmental extracellular matrix by matrix metalloproteinases. In a manner analogous to autophagy, this proline-dependent process for bioenergetics from collagen in extracellular matrix can be designated "ecophagy".
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“In addition to its effects on glutamine metabolism, c-myc-orchestrated remodeling of non-essential amino acid metabolism involves the metabolism of proline (Phang et al., 2008).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Phang et al., 2008
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Matrix metalloproteinases as modulators of inflammation and innate immunity
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Autophagy: molecular machinery for self-eating
Yorimitsu, T., & Klionsky, D. J. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401765 · Cited by 1,566
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Cited by
Sorted by citations
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926
Proline: a multifunctional amino acid
Szabados, L., & Savouré, A. (2009) · Trends in Plant Science · doi:10.1016/j.tplants.2009.11.009 · Cited by 4,351
Amino acids: Metabolism, functions, and nutrition
Wu, G. (2009) · Amino Acids · doi:10.1007/s00726-009-0269-0 · Cited by 3,004
Arginine metabolism and nutrition in growth, health and disease
Wu, G., Bazer, F. W., Davis, T. A., Kim, S. W., Li, P., Marc Rhoads, J., Carey Satterfield, M., Smith, S. B., Spencer, T. E., & Yin, Y. (2009) · Amino Acids · doi:10.1007/s00726-008-0210-y · Cited by 1,362
Proline Mechanisms of Stress Survival
Liang, X., Zhang, L., Natarajan, S. K., & Becker, D. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.5074 · Cited by 1,196
Metadata
- Authors
- Phang, J. M., Donald, S. P., Pandhare, J., & Liu, Y.
- Affiliations
- Frederick National Laboratory for Cancer Research (US)
- National Cancer Institute (US)
- Science Applications International Corporation (United States) (US)
- Corresponding author
- Phang, James M.
- Venue
- Amino Acids
- Published
- 2008-04-10
- Volume
- 35
- Issue
- 4
- Pages
- 681-690
- ISSN
- 0939-4451 (ISSN-L)
- 1438-2199
- OpenAlex
- W1986586503
- Cited by
- 252
- References
- 60
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 8 · 2023: 13 · 2022: 15 · 2021: 20 · 2020: 12 · 2019: 15 · 2018: 15 · 2017: 18 · 2016: 10 · 2015: 15 · 2014: 15 · 2013: 13 · 2012: 11
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- Locations
- Amino Acids (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- Funders
- National Institutes of Health (n01co12400-79-0-22)
- National Cancer Institute (N01CO12400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- proline metabolism, proline oxidase, proline dehydrogenase, cancer metabolism, p53, apoptosis, PPARγ, thiazolidinediones, mTOR, nutritional stress, collagen degradation, matrix metalloproteinases, extracellular matrix, reactive oxygen species, carcinogenesis
- MeSH terms
- Adenosine Triphosphate, Autophagy, Catalysis, Ligands, Models, Biological, Neoplasms, Proline, Proline Oxidase, Protein Kinases, Gene Expression Regulation, Enzymologic, Tumor Suppressor Protein p53, Apoptosis, Thiazolidinediones, PPAR delta, TOR Serine-Threonine Kinases
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