ArticleOncogene2019
PKNOX2 suppresses gastric cancer through the transcriptional activation of IGFBP5 and p53.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- A systematic review of molecular alterations in invasive non-functioning pituitary adenoma.Endocrine · 2022Pooled it
- Prostaglandin ETheranostics · 2019Trial
- CagA promotes gastric cancer stemness and metastasis via DNMT1-mediated epigenetic silencing of BEX1.Cancer gene therapy · 2026Article
- IGF Pathway Components as Potential Biomarkers in Gastric Cancer.International journal of molecular sciences · 2025Article
- HOX and MEINOX in cellular plasticity, fibrosis, and cancer.World journal of stem cells · 2025Review
- CUT&TIME captures the history of open chromatin in developing neurons.bioRxiv : the preprint server for biology · 2025Article
- LncRNA AP001007 protects human renal tubular epithelial HK-2 cells and kidney organoids from LPS-induced injury.Scientific reports · 2024Article
- An attractor state zone precedes neural crest fate in melanoma initiation.bioRxiv : the preprint server for biology · 2024Article
- The role of dysregulated metabolism and associated genes in gastric cancer initiation and development.Translational cancer research · 2024Review
- Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.International journal of molecular sciences · 2024Review
- IGFBP5, as a Prognostic Indicator Promotes Tumor Progression and Correlates with Immune Microenvironment in Glioma.Journal of Cancer · 2024Article
- IDO1-mediated kynurenine production inhibits IGFBP5 signaling to promote 5-fluorouracil-induced senescence escape and chemoresistance in colorectal cancer.American journal of cancer research · 2024Article
- DOT1L promotes expression of CD44 through the Wnt/β-catenin signaling pathway in early gastric carcinoma.Journal of Cancer · 2024Article
- Comprehensive Analyses and Experiments Confirmed IGFBP5 as a Prognostic Predictor Based on an Aging-genomic Landscape Analysis of Ovarian Cancer.Current cancer drug targets · 2024Article
- Secreted insulin-like growth factor binding protein 5 functions as a tumor suppressor and chemosensitizer through inhibiting insulin-like growth factor 1 receptor/protein kinase B pathway in acute myeloid leukemia.Neoplasia (New York, N.Y.) · 2024Article
- Article
- Nucleosome repositioning in chronic lymphocytic leukemia.Genome research · 2023Article
- PKNOX2 suppresses lung cancer cell proliferation by inhibiting the PI3K/AKT/mTOR axis.Experimental and therapeutic medicine · 2023Article
- LncRNAInternational journal of molecular sciences · 2023Article
- CCCTC-Binding Factor Mediates the Transcription of Insulin-Like Growth Factor Binding Protein 5 Through EZH2 in Ulcerative Colitis.Digestive diseases and sciences · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Promoter methylation plays a vital role in tumorigenesis through transcriptional silencing of tumor suppressive genes. Using genome-wide methylation array, we first identified PBX/Knotted Homeobox 2 (PKNOX2) as a candidate tumor suppressor in gastric cancer. PKNOX2 mRNA expression is largely silenced in gastric cancer cell lines and primary gastric cancer via promoter methylation. Promoter methylation of PKNOX2 was associated with poor survival in gastric cancer patients. A series of in vitro and in vivo functional studies revealed that PKNOX2 functions as a tumor suppressor. Ectopic PKNOX2 expression inhibited cell proliferation in GC cell lines and suppressed growth of tumor xenografts in mice via induction of apoptosis and cell cycle arrest; and suppressed cell migration and invasion by blocking epithelial-to-mesenchymal transition. On the other hand, knockdown PKNOX2 in normal gastric epithelial cells triggered diverse malignant phenotypes. Mechanistically, PKNOX2 exerts its tumor suppressive effect by promoting the up-regulation of Insulin like Growth Factor Binding Protein 5 (IGFBP5) and TP53. PKNOX2 binds to the promoter regions of IGFBP5 and TP53 and transcriptionally activated their expression by chromatin immunoprecipitation (ChIP)-PCR assay. IGFBP5 knockdown partly abrogated tumor suppressive effect of PKNOX2, indicating that the function(s) of PKNOX2 are dependent on IGFBP5. IGFBP5 promoted PKNOX2-mediated up-regulation of p53. As a consequence, p53 transcription target genes were coordinately up-regulated in PKNOX2-expressing GC cells, leading to tumor suppression. In summary, our results identified PKNOX2 as a tumor suppressor in gastric cancer by activation of IGFBP5 and p53 signaling pathways. PKNOX2 promoter hypermethylation might be a biomarker for the poor survival of gastric cancer patients.
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