ArticleCell death discovery2024
Deubiquitinase USP9x regulates the proline biosynthesis pathway in non-small cell lung cancer.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed.
- Bosutinib Inhibits USP9X to Suppress the Proliferation, Migration, Angiogenesis and Glycolysis of Hepatocellular Carcinoma Cells by Deubiquitinating PLK1.Clinical and experimental pharmacology & physiology · 2026Article
- Targeting a Unique Cysteine Residue to Achieve Isoform-Selective Inhibition of the Proline Biosynthetic Enzyme Pyrroline-5-Carboxylate Reductase 2.ACS chemical biology · 2026Article
- Ubiquitination and deubiquitination as critical modulators of NSCLC tumorigenesis and drug resistance.Discover oncology · 2026Review
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Metabolic reprogramming and therapeutic targeting in non-small cell lung cancer: emerging insights beyond the Warburg effect.Frontiers in oncology · 2025Review
- USP39 regulates pyruvate handling in non-small cell lung cancer.Cell death discovery · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Metabolic rewiring has been recognized as a hallmark of malignant transformation, supplying the biosynthetic and energetic demands for rapid cancer cell proliferation and tumor progression. A comprehensive understanding of the regulatory mechanisms governing these metabolic processes is still limited. Here, we identify the deubiquitinase ubiquitin-specific peptidase 9 X-linked (USP9x) as a positive regulator of the proline biosynthesis pathway in non-small cell lung cancer (NSCLC). Our findings demonstrate USP9x directly stabilizes pyrroline-5-carboxylate reductase 3 (PYCR3), a key enzyme in the proline cycle. Disruption of proline biosynthesis by either USP9x or PYCR3 knockdown influences the proline cycle leading to a decreased activity of the connected pentose phosphate pathway and mitochondrial respiration. We show that USP9x is elevated in human cancer tissues and its suppression impairs NSCLC growth in vitro and in vivo. Overall, our study uncovers a novel function of USP9x as a regulator of the proline biosynthesis pathway, which impacts lung cancer growth and progression, and implicates a new potential therapeutic avenue.
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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.