ArticleJournal of experimental & clinical cancer research : CR2018
Hypermethylation of DMTN promotes the metastasis of colorectal cancer cells by regulating the actin cytoskeleton through Rac1 signaling activation.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
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- Prognostic Value of Long Non-Coding RNAs GUSB Pseudogene 11 in Colorectal Cancer and Its Regulatory Effect on Tumor Progression.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- RNAseq-based transcriptomics of treatment-naïve multi-inflammatory syndrome in children (MIS-C) demonstrates predominant activation of matrisome, innate and humoral immune pathways.Rheumatology international · 2024Article
- Loss of the polarity protein Par3 promotes dendritic spine neoteny and enhances learning and memory.iScience · 2024Article
- DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.Exploration of targeted anti-tumor therapy · 2024Review
- Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype.Nature communications · 2023Article
- Bayesian Machine Learning Enables Identification of Transcriptional Network Disruptions Associated with Drug-Resistant Prostate Cancer.Cancer research · 2023Article
- Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway ofPathogens (Basel, Switzerland) · 2023Article
- Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status.Cell reports. Medicine · 2023Article
- A Quality Control Mechanism of Splice Site Selection Abrogated under Stress and in Cancer.Cancers · 2022Review
- Bioinformatics Analysis of Prognosis-Related Genes and Expression of CXCL8 in Colorectal Cancer.BioMed research international · 2022Article
- Identification of methylation changes associated with positive and negative growth deviance in Gambian infants using a targeted methyl sequencing approach of genomic DNA.FASEB bioAdvances · 2021Article
- Review
- The Significant Role of the Microfilament System in Tumors.Frontiers in oncology · 2021Review
- Epigenome-wide DNA methylation profiling of portal vein tumor thrombosis (PVTT) tissues in hepatocellular carcinoma patients.Neoplasia (New York, N.Y.) · 2020Article
- Hypomethylation of the cyclin D1 promoter in hepatitis B virus-associated hepatocellular carcinoma.Medicine · 2020Observational
- Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation.Cancer cell international · 2020Article
- Interferon-Induced Protein 44 Correlated With Immune Infiltration Serves as a Potential Prognostic Indicator in Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2020Article
- Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop.Journal of experimental & clinical cancer research : CR · 2019Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundColorectal cancer (CRC) is one of the most common digestive malignant tumors, and DMTN is a transcriptionally differentially expressed gene that was identified using CRC mRNA sequencing data from The Cancer Genome Atlas (TCGA). Our preliminary work suggested that the expression of DMTN was downregulated in CRC, and the Rac1 signaling pathway was significantly enriched in CRC tissues with low DMTN expression. However, the specific functions and underlying molecular mechanisms of DMTN in the progression of CRC and the upstream factors regulating the downregulation of the gene remain unclear.
methodsDMTN expression was analyzed in CRC tissues, and the relationship between DMTN expression and the clinicopathological parameters was analyzed. In vitro and in vivo experimental models were used to detect the effects of DMTN dysregulation on invasion and metastasis of CRC cells. GSEA assay was performed to explore the mechanism of DMTN in invasion and metastasis of CRC. Westernblot, Co-IP and GST-Pull-Down assay were used to detect the interaction between DMTN and ARHGEF2, as well as the activation of the RAC1 signaling. Bisulfite genomic sequence (BSP) assay was used to test the degree of methylation of DMTN gene promoter in CRC tissues.
resultsWe found that the expression of DMTN was significantly decreased in CRC tissues, and the downregulation of DMTN was associated with advanced progression and poor survival and was regarded as an independent predictive factor of CRC patient prognosis. The overexpression of DMTN inhibited, while the knockdown of DMTN promoted, invasion and metastasis in CRC cells. Moreover, hypermethylation and the deletion of DMTN relieved binding to the ARHGEF2 protein, activated the Rac1 signaling pathway, regulated actin cytoskeletal rearrangements, and promoted the invasion and metastasis of CRC cells.
conclusionOur study demonstrated that the downregulation of DMTN promoted the metastasis of colorectal cancer cells by regulating the actin cytoskeleton through RAC1 signaling activation, potentially providing a new therapeutic target to enable cancer precision medicine for CRC patients.
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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.