ArticleCellular oncology (Dordrecht, Netherlands)2021
Blocking MMP-12-modulated epithelial-mesenchymal transition by repurposing penfluridol restrains lung adenocarcinoma metastasis via uPA/uPAR/TGF-β/Akt pathway.
Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 36 citations in OpenAlex.
- IL11 modulates MMP12 expression and cancer cell metastasis via IL11RA/IL6ST-PI3K/Akt/NF-κB pathway in lung cancer.Cell death discovery · 2026Article
- From in-silico QSAR modeling to in-vitro MTT assay: experimental validation of novel uPAR leads for triple-negative breast cancer (TNBC) and skin cancer.Scientific reports · 2026Article
- Molecular and System-Level Characterization of MMP12 Suppression in Lung Cancer: A Combined Bioinformatics and Molecular Approach.International journal of molecular sciences · 2025Article
- Resident Macrophage-Orchestrated Immune and Fibroblast Interactions in Immune Checkpoint Inhibitor-Associated Nephrotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interleukin-1β Inhibits Ovarian Cancer Cell Proliferation and Metastasis Through the MAPK/MMP12 Pathway.International journal of molecular sciences · 2025Article
- Repurposing the antipsychotic drug penfluridol for cancer treatment (Review).Oncology reports · 2024Review
- RON receptor tyrosine kinase as a critical determinant in promoting tumorigenic behaviors of bladder cancer cells through regulating MMP12 and HIF-2α pathways.Cell death & disease · 2024Article
- Single-cell landscape identified SERPINB9 as a key player contributing to stemness and metastasis in non-seminomas.Cell death & disease · 2024Article
- Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.International journal of molecular sciences · 2024Article
- Metabolism-related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation.International wound journal · 2023Article
- Article
- The Emerging Role of MMP12 in the Oral Environment.International journal of molecular sciences · 2023Review
- Genomic and immunogenomic analysis of three prognostic signature genes in LUAD.BMC bioinformatics · 2023Article
- Matrix metalloproteinase 12 is an independent prognostic factor predicting postoperative relapse of conventional renal cell carcinoma - a short report.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.Frontiers in molecular biosciences · 2022Review
- A Potential Anticancer Mechanism of Finger Root (Scientifica · 2022Article
- MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma.Cancer control : journal of the Moffitt Cancer CenterArticle
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 at 5 institutions in 2 countries.
Funding
Abstract
purposeMetastasis of lung adenocarcinoma (LADC) is a crucial factor determining patient survival. Repurposing of the antipsychotic agent penfluridol has been found to be effective in the inhibition of growth of various cancers. As yet, however, the anti-metastatic effect of penfluridol on LADC has rarely been investigated. Herein, we addressed the therapeutic potential of penfluridol on the invasion/metastasis of LADC cells harboring different epidermal growth factor receptor (EGFR) mutation statuses.
methodsMTS viability, transwell migration and invasion, and tumor endothelium adhesion assays were employed to determine cytotoxic and anti-metastatic effects of penfluridol on LADC cells. Protease array, Western blot, immunohistochemistry (IHC), immunofluorescence (IF) staining, and expression knockdown by shRNA or exogenous overexpression by DNA plasmid transfection were performed to explore the underlying mechanisms, both in vitro and in vivo.
resultsWe found that nontoxic concentrations of penfluridol reduced the migration, invasion and adhesion of LADC cells. Protease array screening identified matrix metalloproteinase-12 (MMP-12) as a potential target of penfluridol to modulate the motility and adhesion of LADC cells. In addition, we found that MMP-12 exhibited the most significantly adverse prognostic effect in LADC among 39 cancer types. Mechanistic investigations revealed that penfluridol inhibited the urokinase plasminogen activator (uPA)/uPA receptor/transforming growth factor-β/Akt axis to downregulate MMP-12 expression and, subsequently, reverse MMP-12-induced epithelial-mesenchymal transition (EMT). Subsequent analysis of clinical LADC samples revealed a positive correlation between MMP12 and mesenchymal-related gene expression levels. A lower survival rate was found in LADC patients with a SNAl1
conclusionsOur results indicate that MMP-12 may serve as a useful biomarker for predicting LADC progression and as a promising penfluridol target for treating metastatic LADC.
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.