ArticleOncotarget2016
The essential role of methylthioadenosine phosphorylase in prostate cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Association of Vitamin D receptor Fok I polymorphism with the risk of prostate cancer: a meta-analysis.Oncotarget · 2016Pooled it
- The Methionine-Mitochondria Axis in Cancer: Metabolic Cross-Talk and Therapeutic Vulnerabilities.Current pharmacology reports · 2026Review
- Review
- Resilience and Vulnerabilities of Tumor Cells under Purine Shortage Stress.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Polyamine metabolism in prostate cancer.Current opinion in oncology · 2025Review
- Resilience and vulnerabilities of tumor cells under purine shortage stress.bioRxiv : the preprint server for biology · 2025Article
- Review
- SERS analysis of cancer cell-secreted purines reveals a unique paracrine crosstalk in MTAP-deficient tumors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Polyamines: their significance for maintaining health and contributing to diseases.Cell communication and signaling : CCS · 2023Review
- Activity of pemetrexed in pre-clinical chordoma models and humans.Scientific reports · 2023Article
- MTAP loss: a possible therapeutic approach for glioblastoma.Journal of translational medicine · 2022Review
- Coronary Heart Disease in Type 2 Diabetes Mellitus: Genetic Factors and Their Mechanisms, Gene-Gene, and Gene-Environment Interactions in the Asian Populations.International journal of environmental research and public health · 2022Review
- Polyamine Homeostasis in Development and Disease.Medical sciences (Basel, Switzerland) · 2021Review
- Polyamine pathway activity promotes cysteine essentiality in cancer cells.Nature metabolism · 2020Article
- Article
- Pharmacological polyamine catabolism upregulation with methionine salvage pathway inhibition as an effective prostate cancer therapy.Nature communications · 2020Article
- High Levels of Glutaminase II Pathway Enzymes in Normal and Cancerous Prostate Suggest a Role in 'Glutamine Addiction'.Biomolecules · 2019Article
- 6-Thioguanine and Its Analogs Promote Apoptosis of Castration-Resistant Prostate Cancer Cells in a BRCA2-Dependent Manner.Cancers · 2019Article
- The methionine salvage pathway-involving ADI1 inhibits hepatoma growth by epigenetically altering genes expression via elevating S-adenosylmethionine.Cell death & disease · 2019Article
- Cancer pharmacoprevention: Targeting polyamine metabolism to manage risk factors for colon cancer.The Journal of biological chemistry · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Prostatic epithelial cells secrete high levels of acetylated polyamines into the prostatic lumen. This distinctive characteristic places added strain on the connected pathways, which are forced to increase metabolite production to maintain pools. The methionine salvage pathway recycles the one-carbon unit lost to polyamine biosynthesis back to the methionine cycle, allowing for replenishment of SAM pools providing a mechanism to help mitigate metabolic stress associated with high flux through these pathways. The rate-limiting enzyme involved in this process is methylthioadenosine phosphorylase (MTAP), which, although commonly deleted in many cancers, is protected in prostate cancer. We report near universal retention of MTAP expression in a panel of human prostate cancer cell lines as well as patient samples. Upon metabolic perturbation, prostate cancer cell lines upregulate MTAP and this correlates with recovery of SAM levels. Furthermore, in a mouse model of prostate cancer we find that both normal prostate and diseased prostate maintain higher SAM levels than other tissues, even under increased metabolic stress. Finally, we show that knockdown of MTAP, both genetically and pharmacologically, blocks androgen sensitive prostate cancer growth in vivo. Our findings strongly suggest that the methionine salvage pathway is a major player in homeostatic regulation of metabolite pools in prostate cancer due to their high level of flux through the polyamine biosynthetic pathway. Therefore, this pathway, and specifically the MTAP enzyme, is an attractive therapeutic target for prostate cancer.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.