ArticleOncotarget2016
Epigenetic upregulation of ARL4C, due to DNA hypomethylation in the 3'-untranslated region, promotes tumorigenesis of lung squamous cell carcinoma.
Article in Oncotarget, 2016. 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, 49 citations in OpenAlex.
- Implications of ADP-Ribosylation Factor-Like Protein 4C (ARL4C) in Human Neoplasia With Special Emphasis on Ameloblastoma: A Scoping Review.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Development of ARL4C antisense oligonucleotide with reduced off-target effects and enhanced efficacy as an anti-cancer drug.In vitro cellular & developmental biology. Animal · 2026Article
- Comprehensive analysis acrossiScience · 2025Article
- Immunohistochemistry for Skin Cancers: A Comprehensive Approach to the Diagnosis of Squamous Cell Carcinoma.Cancers · 2025Review
- Small GTPase ARL4C Associated with Various Cancers Affects Microtubule Nucleation.Biomedicines · 2024Article
- Review
- Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- ARL4C is associated with epithelial-to-mesenchymal transition in colorectal cancer.BMC cancer · 2023Article
- Article
- Article
- ARL4C might serve as a prognostic factor and a novel therapeutic target for gastric cancer: bioinformatics analyses and biological experiments.Journal of cellular and molecular medicine · 2021Article
- ADP-Ribosylation Factor Like GTPase 4C (ARL4C) augments stem-like traits of glioblastoma cells by upregulating ALDH1A3.Journal of Cancer · 2021Article
- ARL4C is associated with initiation and progression of lung adenocarcinoma and represents a therapeutic target.Cancer science · 2020Article
- The TRPV4-AKT axis promotes oral squamous cell carcinoma cell proliferation via CaMKII activation.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Role of DNA Methylation in the Resistance to Therapy in Solid Tumors.Frontiers in oncology · 2020Review
- The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective.Frontiers in cell and developmental biology · 2020Review
- Aberrant DNA methylation of synaptophysin is involved in adrenal cortisol-producing adenoma.Aging · 2019Article
- Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development.Scientific reports · 2019Article
- Low-grade myofibroblastic sarcoma arising in the tip of the tongue with intravascular invasion: A case report.Oncology letters · 2018Article
- GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas.Journal of cancer research and clinical oncology · 2017Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ADP-ribosylation factor (ARF)-like 4c (ARL4C) expression, induced by a combination of Wnt/β-catenin and EGF/Ras signaling, has been demonstrated to form epithelial morphogenesis. ARL4C overexpression, due to Wnt/β-catenin and EGF/Ras signaling alterations, was involved in tumorigenesis. It was also reported that ARL4C expression correlates with DNA hypomethylation in the 3'-untranslated region (UTR) of ARL4C gene during lymphogenesis. The current study was conducted to investigate the expression and functions of ARL4C due to DNA hypomethylation in lung and tongue cancers. Immunohistochemical analyses of tissue specimens obtained from lung and tongue squamous cell carcinoma (SCC) patients revealed that ARL4C is not observed in non-tumor regions, but is strongly expressed at high frequencies in tumor lesions. Although inhibition of Wnt/β-catenin or Ras/MAP kinase signaling did not decrease ARL4C expression in NCI-H520 lung SCC cells, ARL4C DNA was clearly hypomethylated in the 3'-UTR. Ten-eleven translocation methylcytosine dioxygenase (TET) enzyme, which mediates DNA demethylation, was highly expressed in NCI-H520 cells. Knockout of TET family proteins (TET1-3) in NCI-H520 cells reduced 5-hydroxymethylcytosine (5hmC) levels and promoted DNA methylation in the 3'-UTR, leading to the decrease in ARL4C expression and ARL4C-mediated cellular migration. In tumor lesions of ARL4C-positive lung SCC, 5hmC was frequently detected and DNA methylation in the 3'-UTR of ARL4C gene was lower than in non-tumor regions, which were consistent with the Cancer Genome Atlas dataset. These results suggest that ARL4C is expressed due to hypomethylation in the 3'-UTR for certain types of cancers and that ARL4C methylation status is involved in cancer cell function.
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