ArticlePloS one2025
Deubiquitination of epidermal growth factor receptor by ubiquitin-specific peptidase 54 enhances drug sensitivity to gefitinib in gefitinib-resistant non-small cell lung cancer cells.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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
2 citing papers in PubMed.
- From EGFR PTM network to TKI resistance: spatial subtypes and targeting in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- The Role of Ubiquitination and Deubiquitination in the Pathogenesis of Acute Kidney Injury: Progress in Research.Biomedicines · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A precise balance between ubiquitination and deubiquitination is crucial for cellular regulation. Ubiquitin-specific peptidase 54 (USP54), an active deubiquitinase (DUB), modulates the ubiquitination of the epidermal growth factor receptor (EGFR). While the significance of USP54 in tumorigenesis is known, its specific function in cancer progression remains unclear. This study investigates the role of USP54 in gefitinib sensitivity in gefitinib-resistant non-small cell lung cancer (NSCLC) cells. Using western blotting and next-generation sequencing, we examined gene expression changes in ubiquitination pathways. USP54 deficiency and its impact on cell viability and gefitinib response were evaluated in 2D and 3D spheroid cancer models. Prolonged gefitinib exposure altered the expression of 20 deubiquitinase-regulating genes. Notably, ubiquitin C-terminal hydrolase L3, downregulated by gefitinib, was identified as a key regulator of EGFR ubiquitination in gefitinib-sensitive PC9 cells. Silencing USP54 in resistant NSCLC cells increased gefitinib-induced EGFR ubiquitination and G0/G1 cell cycle arrest, enhancing drug susceptibility in resistant spheroids. USP54 upregulation in gefitinib-treated cells was associated with reduced EGFR ubiquitination, stabilizing EGFR and promoting cell survival. These findings suggest USP54 as a critical modulator of EGFR stability and a potential therapeutic target to overcome gefitinib resistance in NSCLC.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.