Proline oxidase functions as a mitochondrial tumor suppressor in human cancers
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Tumor metabolism and bioenergetics have become important topics for cancer research and are promising targets for anticancer therapy. Although glucose serves as the main source of energy, proline, an alternative substrate, is important, especially during nutrient stress. Proline oxidase (POX), catalyzing the first step in proline catabolism, is induced by p53 and can regulate cell survival as well as mediate programmed cell death. In a mouse xenograft tumor model, we found that POX greatly reduced tumor formation by causing G2 cell cycle arrest. Furthermore, immunohistochemical staining showed decreased POX expression in tumor tissues. Importantly, HIF-1alpha signaling was impaired with POX expression due to the increased production of alpha-ketoglutarate, a critical substrate for prolyl hydroxylation and degradation of HIF-1alpha. Combined with previous in vitro findings and reported clinical genetic associations, these new findings lead us to propose POX as a mitochondrial tumor suppressor and a potential target for cancer therapy.
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POX expression inhibits tumor cell growth by triggering G2 cell cycle arrest.
“Expression of POX has been shown to inhibit tumor cell growth by triggering cell cycle arrest in the G2 phase (Liu et al., 2009).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Liu et al., 2009
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- Authors
- Liu, Y., Borchert, G. L., Donald, S. P., Diwan, B. A., Anver, M., & Phang, J. M.
- Affiliations
- 1Basic Science Program and
- Frederick National Laboratory for Cancer Research (US)
- Leidos (United States) (US)
- Venue
- Cancer Research
- Published
- 2009-08-12
- Volume
- 69
- Issue
- 16
- Pages
- 6414-6422
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4287397
- OpenAlex
- W2150527694
- Cited by
- 132
- References
- 46
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 16 · 2020: 8 · 2019: 8 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 12 · 2013: 7 · 2012: 12
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institutes of Health (HHSN261200800001C)
- U.S. Public Health Service (HHSN261200800001)
- National Cancer Institute (HHSN261200800001E), Z01BC010743)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- proline oxidase, proline catabolism, p53, HIF-1α, alpha-ketoglutarate, prolyl hydroxylation, G2 cell cycle arrest, cancer metabolism, cancer therapy targets, xenograft tumor model
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Dose-Response Relationship, Drug, Doxorubicin, Humans, Mice, Inbred BALB C, Mice, Nude, Mitochondria, Neoplasms, Proline Oxidase, Tumor Cells, Cultured, Apoptosis, Xenograft Model Antitumor Assays, Tumor Suppressor Proteins, Cell Proliferation, Mice
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