ArticleRespiratory research2025
Mechanism of ECM Stiffness-Integrin-Hippo-ABCG1 axis in regulating ferroptosis and targeted nanodrug intervention in LUAD.
Article in Respiratory research, 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
8 authors.
Funding
Abstract
backgroundRecent advances in mechanobiology have established extracellular matrix (ECM) stiffness as a critical biomechanical cue promoting lung adenocarcinoma (LUAD) metastasis and therapy resistance through mechano-transduction pathways. Ferroptosis is vital in health and disease, regulating LUAD cell death through iron and lipid peroxidation. How mechanical signals are transduced into the electrochemical determinants that govern ferroptosis remains fundamentally unexplored.
methodsLUAD cells were cultured on polyacrylamide (PA) hydrogel of varying stiffness to mimic physiological and pathological ECM conditions. Transcriptome sequencing (RNA-seq) was employed to identify differential expressed genes (DEGs) across varying ECM stiffness conditions, followed by molecular validation of potential regulatory mechanisms through in vitro experiments, in vivo studies, and clinical samples. Based on this mechanistic insight, we aimed to develop nanocarriers for drug encapsulation and assess their therapeutic efficacy in vitro.
resultsOur study have demonstrated that elevated ECM stiffness suppressed ferroptosis in LUAD cells. Mechanistically, high ECM stiffness elevated integrin levels, suppressed the Hippo pathway, and increased YAP levels, which upregulated the downstream molecule ATP-Binding Cassette G1 (ABCG1), thereby reducing ferroptosis sensitivity. This mechanistic model was rigorously validated through a combination of stepwise molecular knockdown experiments in vitro, supporting animal studies in vivo, and analyses of clinical patient samples. Notably, dihydromyricetin (DMY) downregulated ABCG1 expression and sensitized cells to ferroptosis, which was further enhanced by nanocarrier-mediated drug delivery for improved therapeutic outcome.
conclusionOur findings revealed a novel mechanism by which ECM stiffness regulated ferroptosis via the Integrin-Hippo-ABCG1 pathway in LUAD. Nanodrugs designed to target ABCG1 demonstrate significant potential for future LUAD therapy by resensitizing tumors to ferroptosis (Fig. 1).
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.