ArticleJournal of experimental & clinical cancer research : CR2026
Gemcitabine-induced β4 integrin drives cancer progression and gemcitabine resistance in pancreatic cancer.
Article in Journal of experimental & clinical cancer research : CR, 2026. 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
4 authors.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is characterized by high mortality and the frequent emergence of chemoresistance, particularly to gemcitabine (GEM). Recent studies have indicated that tumors exhibit increased malignancy following the acquisition of chemoresistance. However, the underlying molecular mechanisms remain poorly understood. This study aimed to elucidate the mechanisms by which PDAC cells acquire GEM resistance and how this resistance drives cancer progression, focusing on identifying the key molecular drivers involved in these processes.
methodsWe established GEM-resistant PDAC cell lines (GEM-Panc-1 and GEM-MIA PaCa-2) and characterized their malignant phenotypes using migration, invasion, proliferation, and sphere-formation assays, as well as in vivo models for tumor growth, tumor initiation, and metastasis. The functional role of β4 integrin (encoded by ITGB4) was evaluated using stable knockdown and overexpression systems. To investigate the regulatory mechanisms, we employed RNA sequencing, chromatin immunoprecipitation (ChIP), and promoter reporter assays. Clinical relevance was assessed using TCGA datasets and Kaplan‒Meier analysis.
resultsGEM-resistant PDAC cells exhibited enhanced invasive potential, tumorigenicity, and stemness, which coincided with the upregulation of β4 integrin. Knockdown of β4 integrin in GEM-resistant cells attenuated these malignant properties and partially restored GEM sensitivity, whereas its ectopic expression in parental cells conferred aggressive phenotypes. Clinically, high expression of ITGB4 and its ligand, the laminin-332 subunit genes (LAMA3, LAMB3, and LAMC2), correlated with poor overall survival in PDAC patients. Mechanistically, the β4 integrin/laminin-332 axis promoted cell motility and GEM resistance via Src activation. Furthermore, acquired GEM resistance epigenetically supports the activation of ITGB4 transcription, which is associated with β-catenin nuclear translocation and p300-mediated histone H3 acetylation (H3K27ac) at the ITGB4 promoter.
conclusionsOur findings suggest that GEM-induced β4 integrin expression, potentially supported by β-catenin/p300-mediated epigenetic remodeling, is a critical determinant of GEM resistance and PDAC progression. Targeting the β4 integrin/laminin-332/Src signaling axis may provide a promising therapeutic strategy to overcome chemoresistance and improve clinical outcomes in patients with advanced PDAC.
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.