ArticleThe Journal of biological chemistry2024
ATXN3 functions as a tumor suppressor through potentiating galectin-9-mediated apoptosis in human colon adenocarcinoma.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- The Galectin Family in Colorectal Cancer: Integrating Molecular Mechanisms with Diagnostic, Prognostic, and Therapeutic Perspectives.Biomedicines · 2026Review
- TRMT1-mediated tRNA mCell death & disease · 2026Article
- Article
- Hypoxia promotes progression of cervical cancer by modulating the ATXN3-enhanced P53 stability or STAT5 phosphorylation.Cell death discovery · 2026Article
- ATXN3 deubiquitinates ZEB1 and facilitates epithelial-mesenchymal transition in glioblastoma.Scientific reports · 2025Article
- Proteome-Wide Mendelian Randomization Analysis to Identify Potential Plasma Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer Subtypes.International journal of women's health · 2024Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
While deubiquitinase ATXN3 has been implicated as a potential oncogene in various types of human cancers, its role in colon adenocarcinoma remains understudied. Surprisingly, our findings demonstrate that ATXN3 exerts an antitumor effect in human colon cancers through potentiating Galectin-9-induced apoptosis. CRISPR-mediated ATXN3 deletion unexpectedly intensified colon cancer growth both in vitro and in xenograft colon cancers. At the molecular level, we identified ATXN3 as a bona fide deubiquitinase specifically targeting Galectin-9, as ATXN3 interacted with and inhibited Galectin-9 ubiquitination. Consequently, targeted ATXN3 ablation resulted in reduced Galectin-9 protein expression, thereby diminishing Galectin-9-induced colon cancer apoptosis and cell growth arrest. The ectopic expression of Galectin-9 fully reversed the growth of ATXN3-null colon cancer in mice. Furthermore, immunohistochemistry staining revealed a significant reduction in both ATXN3 and Galectin-9 protein expression, along with a positive correlation between them in human colon cancer. Our study identifies the first Galectin-9-specific deubiquitinase and unveils a tumor-suppressive role of ATXN3 in human colon cancer.
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