ArticleCell death & disease2019
ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- Single-Cell Transcriptomic Profiling Identifies B Cell-Intrinsic Dysregulation of Sphingolipid Biosynthesis and Could Be Improved by Inhibiting UGCG in Primary Immune Thrombocytopenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Conserved role of Atx2 in JNK pathway activation.Cell death & disease · 2026Article
- Identification of a novel ion channel-related gene signature to predict prognosis and immune response of gastric cancer.Translational cancer research · 2026Article
- Bioinformatic Analyses of the Ataxin-2 Family Since Algae Emphasize Its Small Isoforms, Large Chimerisms, and the Importance of Human Exon 1B as Target of Therapies to Prevent Neurodegeneration.International journal of molecular sciences · 2026Article
- RBM8A confers oxaliplatin resistance in gastric cancer by maintaining EGFR mRNA stability.Oncogene · 2026Article
- miR-338-3p attenuates oxaliplatin resistance in gastric cancer cells via targeting thrombospondin-1.Archives of medical science : AMS · 2026Article
- Genomic Organization, Evolutionary Conservation and Expression ofBiomedicines · 2025Article
- Stress granules promote quiescence by enhancing p21 levels and reducing phospho-Rb.RNA (New York, N.Y.) · 2025Article
- Effects of flanking regions on DNA i-motif folding and stability.Nucleic acids research · 2025Article
- UBAP2L-driven stress granule formation links oxaliplatin resistance to gastric cancer.Communications biology · 2025Article
- Exosomal FOXL1 from bone marrow mesenchymal stem cells activates the METTL3/ATXN2L pathway to ameliorate high glucose-induced human retinal microvascular endothelial cell injury.Diabetology & metabolic syndrome · 2025Article
- Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Anti-colorectal cancer effects of IRX4 and sensitivity studies to oxaliplatin.Frontiers in immunology · 2025Article
- Repurposing metformin as a potential anticancer agent using in silico technique.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- Myeloid PTEN loss affects the therapeutic response by promoting stress granule assembly and impairing phagocytosis by macrophages in breast cancer.Cell death discovery · 2024Article
- CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes.eLife · 2024Article
- Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) promotes stress granule formation via YBX1 phosphorylation in ovarian cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response.Cancer cell international · 2024Article
- Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin.Biomolecules & therapeutics · 2024Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For gastric cancer (GC) control, metastasis and chemoresistance are the major challenges, accompanied with various stresses. Ataxin-2-like (ATXN2L) was discovered as a novel regulator of stress granules, yet its function in cancers remained unknown. Hence, we wanted to explore the functions of ATXN2L to see whether it participates in stress-related cancer malignant activities. Clinical follow-up was performed to see the impact of ATXN2L on GC patient survival. As a result, ATXN2L expression was upregulated in GC tissue and indicated adverse prognosis for overall survival and recurrence. In GC cells, ATXN2L expression was knocked down and functional experiments were performed. ATXN2L promoted GC cell migration and invasion via epithelial to mesenchymal transition, yet no influence on proliferation was detected by ATXN2L interference. When adding the chemotherapeutic agent oxaliplatin to induce stress, silencing ATXN2L sensitized GC cells to oxaliplatin. Interestingly, oxaliplatin was found to in turn promote ATXN2L expression and stress granule assembly. Then, two acquired oxaliplatin-resistant strains were generated by long-term oxaliplatin induction. The oxaliplatin-resistant strains presented with elevated ATXN2L levels, while silencing ATXN2L in the strains reversed the oxaliplatin resistance by increasing reactive oxygen species production and apoptosis. These results suggested that ATXN2L was responsible for not only intrinsic but also acquired oxaliplatin chemoresistance. Finally, ATXN2L-related signaling was screened using bioinformatic methods, and epidermal growth factor (EGF) was verified to promote ATXN2L expression via PI3K/Akt signaling activation. Blocking EGFR/ATXN2L signaling reversed GC cell oxaliplatin resistance and inhibited migration. In conclusion, ATXN2L promotes cell invasiveness and oxaliplatin resistance and can be upregulated by EGF via PI3K/Akt signaling. ATXN2L may be an indicator and therapeutic target in GC, especially for oxaliplatin-based chemotherapy.
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