ArticleCell death & disease2023
TRIM15 forms a regulatory loop with the AKT/FOXO1 axis and LASP1 to modulate the sensitivity of HCC cells to TKIs.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- CRISPR Screen Reveals Pathways and Factors Driving Tyrosine Kinase Inhibitor Resistance in Hepatocellular Carcinoma.Cancer medicine · 2026Article
- ZDHHC9-Mediated Palmitoylation of ACSL4 Drives Ferroptosis in Diabetes Mellitus-Induced Erectile Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PPARα activation alleviates lithocholic acid-induced liver injury by inhibiting pyroptosis.Liver research (Beijing, China) · 2026Article
- Obesity-Associated TRIM15 Promotes the Proliferation of Esophageal Adenocarcinoma Through the YY2/FOXRED1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- Exploring the TRIM15 protein interaction network as a drug target using machine learning in pancreatic cancer.Discover oncology · 2025Article
- Integrative Epigenomic and Targeted Protein Analysis in MRONJ: Correlating DNA Methylation with Bone Biomarkers.International journal of molecular sciences · 2025Article
- N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer.Journal of translational medicine · 2025Article
- Article
- Review
- The Role of Tripartite Motif Family Proteins in Chronic Liver Diseases: Molecular Mechanisms and Therapeutic Potential.Biomolecules · 2024Review
- Emerging roles of tripartite motif family proteins (TRIMs) in breast cancer.Cancer medicine · 2024Review
- TRIM5 as a promising diagnostic biomarker of hepatocellular carcinoma: integrated analysis and experimental validation.Functional & integrative genomics · 2024Article
- ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma.Cancer research · 2023Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For patients with advanced or metastatic Hepatocellular carcinoma (HCC) who are not suitable for surgical resection, systemic therapy has been considered to be the standard treatment. In recent years, a small subset of patients with unresectable HCC have been benefit from tyrosine kinase inhibitors (TKIs), and the overall survival time of these patients is significantly increased. However, all responders ultimately develop resistance to TKI treatment. The tripartite motif (TRIM) family member TRIM15 acts as an E3 ligase to mediate the polyubiquitination of substrates in cells. However, the biological role of TRIM15 in HCC is still an enigma. In our study, our results demonstrated that TRIM15 was abnormally upregulated in liver cancer cells after treated with TKIs and that this upregulation of TRIM15 contributed to TKI resistance in liver cancer cells. Then, we demonstrated that the upregulation of TRIM15 after TKI treatment was mediated by the AKT/FOXO1 axis. Moreover, we demonstrated that TRIM15 induced the nuclear translocation of LASP1 by mediating its K63-linked polyubiquitination, which modulated sensitivity to TKIs by increasing the phosphorylation of AKT and the expression of Snail in liver cancer cells. Collectively, we identified a novel AKT/FOXO1/TRIM15/LASP1 loop in cells, which provided potential candidates for overcoming TKI resistance in HCC.
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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 Socratic graph.