ArticleCancer cell international2025
CUL2 confers ferroptosis resistance in pancreatic cancer by disrupting KEAP1-mediated NRF2 degradation.
Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundPancreatic cancer (PC) is characterized by high chemoresistance and poor prognosis. CUL2, a scaffold protein of E3 ubiquitin ligases, has been implicated in tumor progression, but its role in PC remains unclear.
methodsCUL2 expression was analyzed in PC tissues and cell lines using TCGA and GEO datasets, qRT-PCR, Western blot, and immunohistochemistry analysis. The biological functions of CUL2 were investigated through gain- and loss-of-function studies in vitro. The impact of CUL2 overexpression on gemcitabine sensitivity was evaluated in xenograft models. Molecular mechanisms were explored using proteasome inhibitor MG132, co-immunoprecipitation, subcellular fractionation, and ferroptosis assessment.
resultsCUL2 was significantly upregulated in PC tissues and correlated with poor prognosis. CUL2 promoted PC cell proliferation, migration, and EMT. Mechanistically, CUL2 competed with NRF2 for KEAP1 binding, thereby preventing KEAP1-mediated NRF2 degradation and promoting NRF2 nuclear translocation. CUL2 promoted oxidative stress while activating NRF2-dependent antioxidant response. The CUL2-NRF2 axis suppressed ferroptosis and conferred gemcitabine resistance in PC cells. In xenograft models, CUL2 overexpression enhanced tumor growth and attenuated gemcitabine sensitivity through NRF2-mediated ferroptosis inhibition.
conclusionsOur findings reveal a novel mechanism whereby CUL2 promotes PC progression and ferroptosis resistance through regulation of the KEAP1-NRF2 axis. CUL2 overexpression enhances cellular antioxidant capacity and maintains mitochondrial integrity, thereby conferring broad resistance to ferroptosis-inducing conditions. This study suggests that targeting the CUL2-NRF2 axis to enhance ferroptosis sensitivity might represent a promising therapeutic strategy for PC treatment.
Indexed as
Identifiers
What Socratic holds
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.