ArticleJournal of experimental & clinical cancer research : CR2024
TrkA promotes MDM2-mediated AGPS ubiquitination and degradation to trigger prostate cancer progression.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Evaluation of translational potential of mRNA vaccine candidate antigens for pancreatic cancer: a systematic review based on clinical evidence and stratified prioritization strategies.Frontiers in immunology · 2026Pooled it
- Ferroptosis and prostate cancer: A translational path from molecular mechanisms to precision therapy.Genes & diseases · 2026Review
- Deubiquitinases at the crossroads of ferroptosis and cancer therapy: mechanisms and therapeutic potential.Molecular biology reports · 2026Review
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- Integrated regulation of ferroptosis in prostate cancer covering mechanisms, resistance, and translational opportunities.Journal of molecular medicine (Berlin, Germany) · 2026Review
- A Ubiquitination-Related Gene Prognostic Signature and the Oncogenic Role of RNF149 in Nasopharyngeal Carcinoma: scRNAseq- Based Bioinformatics and Experimental Validation.Current medicinal chemistry · 2026Article
- Review
- From biosynthesis to function: the roles of ether lipids in cancer development and treatment.Lipids in health and disease · 2025Review
- From foe to friend: Rewiring oncogenic pathways through artificial selenoprotein to combat immune-resistant tumor.Journal of pharmaceutical analysis · 2025Article
- Reduced ALDH1A1 expression in multiple myeloma cells increases resistance to daratumumab via downregulation of retinoic acid.Cellular and molecular life sciences : CMLS · 2025Article
- Investigation of key ferroptosis-associated genes and potential therapeutic drugs for asthma based on machine learning and regression models.Scientific reports · 2025Article
- Review
- The alkylglycerone phosphate synthase sustains the resistance of gastric cancer cells to ferroptosis induced by Apatinib.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- ML210 Antagonizes ABCB1- Not ABCG2-Mediated Multidrug Resistance in Colorectal Cancer.Biomedicines · 2025Article
- Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- The role of ubiquitination and deubiquitination in urological tumours.Frontiers in pharmacology · 2025Review
- The ubiquitin ligase RCBTB2 regulates aggrephagy and inhibits prostate cancer progression by targeting GPAA1 for degradation.American journal of cancer research · 2025Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAs a novel necrosis manner, ferroptosis has been increasingly reported to play a role in tumor progression and treatment, however, the specific mechanisms underlying its development in prostate cancer remain unclear. Growing evidence showed that peroxisome plays a key role in ferroptosis. Herein, we identified a novel mechanism for the involvement of ferroptosis in prostate cancer progression, which may provide a new strategy for clinical treatment of prostate cancer.
methodsLabel-Free Mass spectrometry was used to screen and identify candidate proteins after ferroptosis inducer-ML210 treatment. Immunohistochemistry was undertaken to explore the protein expression of AGPS in prostate cancer tissues compared with normal tissues. Co-immunoprecipitation and GST pull-down were used to identify the directly binding of AGPS to MDM2 in vivo and in vitro. CCK8 assay and colony formation assay were used to illustrate the key role of AGPS in the progression of prostate cancer in vitro. The xenograft model was established to verify the key role of AGPS in the progression of prostate cancer in vivo.
resultsAGPS protein expression was downregulated in prostate cancer tissues compared with normal tissues from the first affiliated hospital of Zhengzhou University dataset. Lower expression was correlated with poorer overall survival of patients compared to those with high expression of AGPS. In addition, AGPS can promote ferroptosis by modulating the function of peroxisome-resulting in the lower survival of prostate cancer cells. Furthermore, it was shown that AGPS can be ubiquitinated and degraded by the E3 ligase-MDM2 through the proteasomal pathway. Meanwhile, kinase TrkA can promote the combination of AGPS and MDM2 by phosphorylating AGPS at Y451 site. It was verified that kinase TrkA inhibitor-Larotrectinib can increase the susceptibility of prostate cancer cells to ferroptosis, which leads to the inhibition of prostate cancer proliferation to a great extent in vitro and in vivo.
conclusionBased on these findings, we proposed the combination of ferroptosis inducer and TrkA inhibitor to synergistically exert anti-tumor effects, which may provide a new strategy for the clinical treatment of prostate cancer.
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