ArticleCellular oncology (Dordrecht, Netherlands)2020
Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.
Article in Cellular oncology (Dordrecht, Netherlands), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
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- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- Network-Based Prediction of Oligodendroglioma Driver Gene Candidates within the Region of the 1p/19q Co-deletion Utilizing Single-Cell Transcriptomes.Computational and structural biotechnology journal · 2026Article
- Examining the Role of Matrix Metalloproteinase-2 and MicroRNAs Regulation in Breast Cancer.The breast journal · 2025Review
- SPINT2 is involved in the proliferation, migration and phenotypic switching of aortic smooth muscle cells: Implications for the pathogenesis of thoracic aortic dissection.Experimental and therapeutic medicine · 2023Article
- Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer.Scientific reports · 2023Article
- Identification and validation of a seven-gene prognostic marker in colon cancer based on single-cell transcriptome analysis.IET systems biology · 2022Article
- Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like SynoviocytesFrontiers in immunology · 2021Article
- Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma.Genes · 2020Article
Corrections and comments
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Authors and funding
16 authors at 10 institutions in 3 countries.
Funding
Abstract
purposeHigh-grade gliomas (HGG) remain one of the most aggressive tumors, which is primarily due to its diffuse infiltrative nature. Serine proteases and metalloproteases are known to play key roles in cellular migration and invasion mechanisms. SPINT2, also known as HAI-2, is an important serine protease inhibitor that can affect MET signaling. SPINT2 has been found to be frequently downregulated in various tumors, whereby hypermethylation of its promoter appears to serve as a common mechanism. Here, we assessed the clinical relevance of SPINT2 expression and promoter hypermethylation in pediatric and adult HGG and explored its functional role.
methodsA series of 371 adult and 77 pediatric primary HGG samples was assessed for SPINT2 protein expression (immunohistochemistry) and promoter methylation (methylation-specific PCR) patterns. After SPINT2 knockdown and knock-in in adult and pediatric HGG cell lines, a variety of in vitro assays was carried out to determine the role of SPINT2 in glioma cell viability and invasion, as well as their mechanistic associations with metalloprotease activities.
resultsWe found that SPINT2 protein expression was frequently absent in adult (85.3%) and pediatric (100%) HGG samples. The SPINT2 gene promoter was found to be hypermethylated in approximately half of both adult and pediatric gliomas. Through functional assays we revealed a suppressor activity of SPINT2 in glioma cell proliferation and viability, as well as in their migration and invasion. These functions appear to be mediated in part by MMP2 expression and activity.
conclusionsWe conclude that dysregulation of SPINT2 is a common event in both pediatric and adult HGG, in which SPINT2 may act as a tumor suppressor.
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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 Socratic graph.