ArticleMolecular therapy. Nucleic acids2017
A Novel Pak1/ATF2/miR-132 Signaling Axis Is Involved in the Hematogenous Metastasis of Gastric Cancer Cells.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting PAK1 suppresses tumor progression by promoting mRNA decay of oncogenic factors and enhancing chemotherapeutic efficacy in colorectal cancer.Genes & diseases · 2026Article
- A novel PAK1/TCF1 regulatory axis promotes non-small cell lung cancer progression.Discover oncology · 2025Article
- The ATF2/miR-3913-5p/CREB5 axis is involved in the cell proliferation and metastasis of colorectal cancer.Communications biology · 2023Article
- Review
- The Characterization and Differential Analysis of mAnimals : an open access journal from MDPI · 2023Article
- Article
- Review
- The two-faced role of ATF2 on cisplatin response in gastric cancer depends on p53 context.Cell & bioscience · 2022Article
- LINC01232 Promotes Metastasis and EMT by Regulating miR-506-5p/PAK1 Axis in Gastric Cancer.Cancer management and research · 2022Article
- Protective effect of LNA-anti-miR-132 therapy on liver fibrosis in mice.Molecular therapy. Nucleic acids · 2021Article
- Molecular mechanisms of the microRNA-132 during tumor progressions.Cancer cell international · 2021Review
- Review
- Blockage of PAK1 alleviates the proliferation and invasion of NSCLC cells via inhibiting ERK and AKT signaling activity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes.Molecular therapy. Nucleic acids · 2020Article
- Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma.Journal of cellular and molecular medicine · 2020Article
- A PTAL-miR-101-FN1 Axis Promotes EMT and Invasion-Metastasis in Serous Ovarian Cancer.Molecular therapy oncolytics · 2020Article
- Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression.Frontiers in oncology · 2020Article
- P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer.Theranostics · 2020Review
- A 3-MicroRNA Signature Identified From Serum Predicts Clinical Outcome of the Locally Advanced Gastric Cancer.Frontiers in oncology · 2020Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We, along with others, have shown previously that P21-activated kinase 1 (Pak1) plays a pivotal role in gastric cancer progression and metastasis. However, whether Pak1 controls gastric cancer metastasis by regulating microRNAs (miRNAs) has never been explored. Here, we report a novel mechanism of Pak1 in tumor metastasis. A detailed examination revealed that Pak1 interacts with and phosphorylates the serine 62 residue of ATF2 and then blocks its translocation into the nucleus. We also confirmed that ATF2 binds to the promoter of miR-132 and tightly regulates its transcription, thus explaining the regulatory mechanism of miR-132 by Pak1. miR-132 also significantly reduced cell adhesion, migration, and invasion of gastric cancer cells in vitro and significantly prevented tumor metastasis in vivo. miR-132 specifically inhibited hematogenous metastasis, but not lymph node or implantation metastases. In order to further delineate the effects of the Pak1/ATF2/miR-132 cascade on gastric cancer progression, we identified several targets of miR-132 using a bioinformatics TargetScan algorithm. Notably, miR-132 reduced the expression of CD44 and fibronectin1 (FN1), and such inhibition enabled lymphocytes to home in on gastric cancer cells and induce tumor apoptosis. Taken together, our studies establish a novel cell-signaling pathway and open new possibilities for therapeutic intervention of gastric cancer.
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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.