ArticleRedox biology2019
aPKCι promotes gallbladder cancer tumorigenesis and gemcitabine resistance by competing with Nrf2 for binding to Keap1.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Bile metabolite palmitic acid augments the migration of gallbladder cancer cells through the ROS/NF-кB signaling pathway.Scientific reports · 2025Article
- High Expression ofCancer genomics & proteomics · 2025Article
- RTA 408 attenuates TBHP-Induced apoptosis in nucleus pulposus cells via Nrf2/ARE and NF-κB signaling pathways: in vitro and in vivo evidence for mitigating rats' intervertebral disc degeneration.Arthritis research & therapy · 2025Article
- Discovery of a molecular glue for EGFR degradation.Oncogene · 2025Article
- Targeted gene sequencing and bioinformatics analysis of patients with gallbladder neuroendocrine carcinoma: A case report.World journal of gastrointestinal oncology · 2025Article
- DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells.Redox biology · 2024Article
- Nrf2 activation by pyrroloquinoline quinone inhibits natural aging-related intervertebral disk degeneration in mice.Aging cell · 2024Article
- Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.Chinese medicine · 2024Article
- The Role of Nrf2 in the Regulation of Mitochondrial Function and Ferroptosis in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Troponin T1 in tumorigenesis and immune modulation: Insights into multiple cancers and kidney renal clear cell carcinoma.Journal of cellular and molecular medicine · 2024Article
- Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation.Aging cell · 2023Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights.Experimental & molecular medicine · 2022Review
- E3 ligase TRIM15 facilitates non-small cell lung cancer progression through mediating Keap1-Nrf2 signaling pathway.Cell communication and signaling : CCS · 2022Article
- KIFC3 Promotes Proliferation, Migration, and Invasion in Colorectal CancerFrontiers in genetics · 2022Article
- Prognostic value of a novel glycolysis-related gene expression signature for gastrointestinal cancer in the Asian population.Cancer cell international · 2021Article
- Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas.Frontiers in pharmacology · 2021Article
- The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging.Oxidative medicine and cellular longevity · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gallbladder cancer (GBC) is a highly malignant bile duct cancer with poor prognosis characterized by its insensitivity to chemotherapy. Emerging evidence indicates that cytoprotective antioxidation is involved in drug resistance of various cancers; however, the underlying molecular mechanisms remain obscure. Here, we demonstrated that atypical protein kinase Cι (aPKCι) mediated reactive oxygen species (ROS) inhibition in a kinase-independent manner, which played a crucial role in tumorigenesis and chemoresistance. Mechanistically, we found that aPKCι facilitated nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation, nuclear translocation and activated its target genes by competing with Nrf2 for binding to Kelch-like ECH-associated protein 1 (Keap1) through a highly conserved DLL motif. In addition, the aPKCι-Keap1 interaction was required for antioxidant effect, cell growth and gemcitabine resistance in GBC. Importantly, we further confirmed that aPKCι was frequently upregulated and correlated with poor prognosis in patients with GBC. Collectively, our findings suggested that aPKCι positively modulated the Keap1-Nrf2 pathway to enhance GBC growth and gemcitabine resistance, implying that the aPKCι-Keap1-Nrf2 axis may be a potential approach to overcome the drug resistance for the treatment of GBC.
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Registered trials
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.