ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
PIP5K1A Suppresses Ferroptosis and Induces Sorafenib Resistance by Stabilizing NRF2 in Hepatocellular Carcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- Brief report: Therapeutic benefit of ISA-2011B in colorectal cancer.Molecular biology reports · 2026Article
- PDIA6 exacerbates hepatocellular carcinoma via enhancing proteasome-dependent degradation of AKAP12.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- SERPINE2-mediated activation of JAK2/STAT3 facilitates NRF2 nuclear translocation and GCLC transcription to confer ferroptosis resistance and lenvatinib resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- TSC22D4 drives clear cell renal cell carcinoma progression and therapy resistance by stabilizing NRF2 through KEAP1 disruption.Cell death & disease · 2026Article
- Nrf2/NOX2 Pathway Dysregulation and Oxidative Stress Biomarkers in Gaucher Disease-Associated Parkinsonism: Insights Into a Potential Therapeutic Target.Journal of cellular and molecular medicine · 2026Article
- NUP93 facilitates the nuclear import of SOX2 to activate G3BP1 transcription and impairs gemcitabine response in pancreatic cancer.Cell death & disease · 2026Article
- Ferroptosis-autophagy crosstalk in bladder cancer: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Long non-coding RNA LINC00092 inhibits esophageal squamous cell carcinoma progression by promoting ferroptosis through the MAZ/NFE2L2 axis.Journal of thoracic disease · 2026Article
- Post-Translational Modification Networks in Ferroptosis: Orchestrating Defense, Drug Resistance, and Therapeutic Opportunities in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Inhibiting SSBP1 enhances ferroptosis and improves the effectiveness of sorafenib treatment for liver cancer.International journal of oncology · 2025Article
- PIP5K1A Suppresses Ferroptosis and Induces Sorafenib Resistance by Stabilizing NRF2 in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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10 authors.
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Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has emerged as a promising strategy for cancer treatment. However, the development of ferroptosis resistance limits the efficacy of such treatments. This study reports that phosphatidylinositol 4-phosphate 5-kinase 1 alpha (PIP5K1A) promotes HCC tumorigenesis and predicts poor prognosis in HCC patients. Knockdown of PIP5K1A enhances lipid peroxidation and increases sensitivity to sorafenib-induced ferroptosis by inhibiting the activation of downstream ferroptosis-related genes regulated by nuclear factor erythroid-2-related factor 2 (NRF2). Mechanistically, PIP5K1A competitively binds to the Kelch domain of Kelch-like ECH-associated protein 1 in a kinase-independent manner, leading to NRF2 escaping from ubiquitination degradation, thereby promoting NRF2-dependent transcription and suppressing ferroptosis. Furthermore, ISA-2011B, a PIP5K1A-specific inhibitor, effectively inhibits HCC growth and sensitized HCC cells to sorafenib. In conclusion, PIP5K1A is a promising therapeutic target for improving the efficacy of sorafenib and other ferroptosis inducers in HCC.
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