ArticleCell death & disease2012
Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed, 88 citations in OpenAlex.
- Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus.Nature communications · 2025Article
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4.Communications biology · 2025Article
- Forms of Non-Apoptotic Cell Death and Their Role in Gliomas-Presentation of the Current State of Knowledge.Biomedicines · 2024Review
- PAK4 inhibition augments anti-tumour effect by immunomodulation in oral squamous cell carcinoma.Scientific reports · 2024Article
- FOSL1's Oncogene Roles in Glioma/Glioma Stem Cells and Tumorigenesis: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Calcitriol Suppressed Isoproterenol-induced Proliferation of Cardiac Fibroblasts via Integrin β3/FAK/Akt Pathway.Current medical science · 2023Article
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- A Bioinformatics-Based Analysis of an Anoikis-Related Gene Signature Predicts the Prognosis of Patients with Low-Grade Gliomas.Brain sciences · 2022Article
- Targeting of p21-Activated Kinase 4 Radiosensitizes Glioblastoma Cells via Impaired DNA Repair.Cells · 2022Article
- Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?Pharmaceutics · 2022Review
- A Study on the Effect of the Substituent against PAK4 Inhibition Using In Silico Methods.International journal of molecular sciences · 2022Article
- Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.Frontiers in oncology · 2022Review
- Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition.Cancer chemotherapy and pharmacology · 2021Article
- Potential Antimicrobial Activity of Galloyl-Flavonoid Glycosides FromFrontiers in microbiology · 2021Article
- Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Review
- Recent Trends of microRNA Significance in Pediatric Population Glioblastoma and Current Knowledge of Micro RNA Function in Glioblastoma Multiforme.International journal of molecular sciences · 2020Review
- Glioblastoma Cell Resistance to EGFR and MET Inhibition Can Be Overcome via Blockade of FGFR-SPRY2 Bypass Signaling.Cell reports · 2020Article
- PD-L1/PD-1 Axis in Glioblastoma Multiforme.International journal of molecular sciences · 2019Review
- Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Gliomas display anoikis resistance, enhanced invasion in to the adjacent brain parenchyma and eventually recur despite using the standard therapies. Our studies on increased anoikis sensitization in matrix metalloproteinase-2 (MMP-2)-knockdown 4910 and 5310 human glioma xenograft cells were interestingly correlated with p21-activated kinase 4 (PAK4) inhibition, prompting us to further investigate the role of PAK4 in glioma. Here, we report the PAK4 upregulation in positive correlation with increasing glioma pathological grades. The siRNA-mediated PAK4 knockdown elevated anoikis, and inhibited invasion and migration by downregulating MMP-2, αvβ3-integrin and phospho-epidermal growth factor receptor (phospho-EGFR). The cDNA-PCR arrays revealed a transcriptional suppression of essential proteins involved in cell proliferation and adhesion in PAK4-knockdown cells. Most importantly, glutathione S-transferase pull-down assays demonstrated the MMP-2 as a new PAK4-interacting protein which binds to PAK4 kinase domain. Individual EGFR/ErbB2 inhibitor and αvβ3 antibody treatments in PAK4si-treated cells indicated the regulation of αvβ3/EGFR survival signaling by PAK4. Overexpression of PAK4 significantly reversed the MMP2si-induced cell death in both cell lines. Codepletion of PAK4 and MMP-2 resulted in robust anoikis-mediated cell death, and severely inhibited invasive and migratory properties in these cells. PAK4si inhibited in vivo tumor growth in nude mice by inhibiting MMP-2, β3-integrin and phospho-EGFR levels in tumors. Our findings indicate a physical association between PAK4 and MMP-2, and suggest the future therapeutic potential of PAK4/MMP-2 dual targeting in glioma treatment.
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.