ArticleSignal transduction and targeted therapy2024
Josephin domain containing 2 (JOSD2) promotes lung cancer by inhibiting LKB1 (Liver kinase B1) activity.
Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting JOSD2 degrades β-catenin to suppress colorectal cancer metastasis by disrupting RAS/ERK/β-catenin axis.Acta pharmacologica Sinica · 2026Article
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Rewiring KRAS-driven cancers through the ubiquitin-proteasome system: therapeutic opportunities with a focus on deubiquitinase.Experimental & molecular medicine · 2026Review
- S100A6 promotes liver metastasis by activating FGFR3 signaling in BAP1-deficient uveal melanoma.Oncogene · 2026Article
- Medicinal Plant Seeds in Nutritional Oncology: An Integrative Review of Emerging Therapeutics for Non-Small Cell Lung Cancer.Current nutrition reports · 2026Review
- From concept to application: Exploring the evolution and potential of DUBTAC technology.Acta pharmaceutica Sinica. B · 2026Review
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- USP10-mediated deubiquitination and activation ofActa pharmaceutica Sinica. B · 2026Article
- Deubiquitinating enzyme JOSD2 modulates cGAS to facilitate immune evasion in colorectal cancer.Oncoimmunology · 2025Article
- Identification of AKOS, a Chikungunya virus inhibitor, as a USP14 inhibitor for colorectal cancer treatment.Acta pharmacologica Sinica · 2025Article
- Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall.International journal of molecular sciences · 2025Article
- JOSD2 alleviates acute kidney injury through deubiquitinating SIRT7 and negativity regulating SIRT7-NF-κB inflammatory pathway in renal tubular epithelial cells.Acta pharmacologica Sinica · 2025Article
- VCP Promotes Cholangiocarcinoma Development by Mediating BAP1 Ubiquitination-Dependent Degradation.Cancer science · 2025Article
- Josephin Domain Containing 2 (JOSD2) inhibition as Pan-KRAS-mutation-targeting strategy for colorectal cancer.Nature communications · 2025Article
- Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- Loss of USP10 promotes hepatocellular carcinoma proliferation by regulating the serine synthesis pathway through inhibition of LKB1 activity.Cancer science · 2024Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-small cell lung cancer (NSCLC) ranks as one of the leading causes of cancer-related deaths worldwide. Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment, these drugs are suitable for and beneficial to a mere ~30% of NSCLC patients. Consequently, the need for novel strategies addressing NSCLC remains pressing. Deubiquitinases (DUBs), a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets. Nevertheless, the mechanisms by which DUBs promote NSCLC remain poorly understood. Through a global analysis of the 97 DUBs' contribution to NSCLC survival possibilities using The Cancer Genome Atlas (TCGA) database, we found that high expression of Josephin Domain-containing protein 2 (JOSD2) predicted the poor prognosis of patients. Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo. Mechanically, we found that JOSD2 restricts the kinase activity of LKB1, an important tumor suppressor generally inactivated in NSCLC, by removing K6-linked polyubiquitination, an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex. Notably, we identified the first small-molecule inhibitor of JOSD2, and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo. Our findings highlight the vital role of JOSD2 in hindering LKB1 activity, underscoring the therapeutic potential of targeting JOSD2 in NSCLC, especially in those with inactivated LKB1, and presenting its inhibitors as a promising strategy for NSCLC treatment.
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