Wnt/β-catenin-YAP axis may be involved in primary intraosseous carcinoma, NOS, arising from odontogenic keratocyst
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1064633 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Odontogenic tumors (OGTs), which originate from cells of odontogenic apparatus and their remnants, are rare entities. Primary intraosseous carcinoma, NOS (PIOC), is one of the OGTs, but it is even rarer and has a worse prognosis. The characteristics of PIOC, especially in immunohistochemical features and its pathogenesis, remain unclear. We characterized a case of PIOC arising from the left mandible, in which histopathological findings showed a transition between the odontogenic keratocyst and the carcinoma. The tumorous lesion of this PIOC exhibited malignant potentials with an invasive growth of carcinoma cells into the bone tissue, an elevated Ki-67 index, and lower signal for CK13 and higher signal for CK17 compared with the non-tumor region, histopathologically and immunohistopathologically. Further immunohistochemical analyses demonstrated increased expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C) (accompanying expression of β-catenin in the nucleus) and yes-associated protein (YAP) in the tumorous lesion. On the other hand, YAP was expressed and the expression of ARL4C was hardly detected in the non-tumor region. In addition, quantitative RT-PCR analysis using RNAs and dot blot analysis using genomic DNA showed the activation of Wnt/β-catenin signaling and epigenetic alterations, such as an increase of 5mC levels and a decrease of 5hmC levels, in the tumorous lesion. A DNA microarray and gene ontology analysis demonstrated that numerous gene expression variations and signal activation, including Notch signaling, were altered in non-tumor and tumor lesions within this PIOC. Experiments with the GSK-3 inhibitor revealed that β-catenin pathway increased not only mRNA levels of ankyrin repeat domain1 (ANKRD1) but also protein levels of YAP and TAZ in oral squamous cell carcinoma cell lines. These results suggested that further activation of YAP signaling by Wnt/β-catenin signaling may be associated with the development of PIOC arising from odontogenic keratocyst in which YAP signaling is activated.
2024-01-26 | GSE253232 | GEO
Project description:Ameloblastoma (AM) is a benign but locally invasive tumor with high recurrence rates. Invasive behavior of the odontogenic tumor results in destruction of the adjacent jawbone and formation of daughter cysts, hindering the complete elimination of cancer cells during surgery. To understand the underlying mechanism of AM invasion, we compared the transcriptome of AM with that of an odontogenic keratocyst (OKC), a dental epithelium-originated cyst with non-invasive characteristics.
2022-05-02 | GSE186489 | GEO
Project description:The aim of this study was to decode the gene expression program characterizing odontogenic keratocyst (OKC) development, by performing a comprehensive transcriptomics analysis applied on whole OKC tissue derived from sporadic and Basal Cell Nevus Syndrome (BCNS)-associated OKCs, and control samples of pericoronal tissues of impacted teeth (dental follicles, DFs) derived from healthy individuals.
2022-06-22 | GSE180706 | GEO
Project description:Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into the cellular and molecular pathways implicated in human dental cysts. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and -extrinsic stressors. With an atlas of single-cell RNA sequencing and spatial transcriptomics, cellular senescence and its effects were investigated, with a focus on epithelial cells of odontogenic keratocyst.
2026-05-20 | GSE304124 | GEO
Project description:Ameloblastoma is a locally aggressive odontogenic epithelial tumor with poorly understood intraosseous pathogenesis due to a lack of physiologically relevant models. Here, we established an orthotopic intraosseous mouse model using ameloblastoma epithelial cells in combination with ameloblastoma-derived mesenchymal stromal cells (AMMSCs) or their secretome. AMMSC-derived extracellular vesicle-enriched secretome enhances stemness, epithelial-mesenchymal transition (EMT) phenotypes, and tumorigenic ability of ameloblastoma epithelial cells. A unique signature of microRNAs in AMMSC-derived secretome is functionally associated with the upregulation of EMT-regulatory transcription factors in tumor epithelial cells. Single-nucleus ATAC and RNA sequencing revealed a dynamic EMT trajectory in primary human AM-derived epithelial cells activated by paired AMMSC-derived secretome. This study suggests that AMMSCs and their secretome drive orthotopic AM tumor development by promoting tumor epithelial cell proliferation, EMT, and vascular formation in the tumor microenvironment. This stromal-oriented orthotopic model provides a clinically relevant platform for dissecting tumor-stroma crosstalk and identifying therapeutic vulnerabilities in ameloblastoma.
2026-08-09 | GSE317374 | GEO
Project description:Ameloblastoma is a locally aggressive odontogenic epithelial tumor with poorly understood intraosseous pathogenesis due to a lack of physiologically relevant models. Here, we established an orthotopic intraosseous mouse model using ameloblastoma epithelial cells in combination with ameloblastoma-derived mesenchymal stromal cells (AMMSCs) or their secretome. AMMSC-derived extracellular vesicle-enriched secretome enhances stemness, epithelial-mesenchymal transition (EMT) phenotypes, and tumorigenic ability of ameloblastoma epithelial cells. A unique signature of microRNAs in AMMSC-derived secretome is functionally associated with the upregulation of EMT-regulatory transcription factors in tumor epithelial cells. Single-nucleus ATAC and RNA sequencing revealed a dynamic EMT trajectory in primary human AM-derived epithelial cells activated by paired AMMSC-derived secretome. This study suggests that AMMSCs and their secretome drive orthotopic AM tumor development by promoting tumor epithelial cell proliferation, EMT, and vascular formation in the tumor microenvironment. This stromal-oriented orthotopic model provides a clinically relevant platform for dissecting tumor-stroma crosstalk and identifying therapeutic vulnerabilities in ameloblastoma.
2026-08-09 | GSE317373 | GEO
Project description:Ameloblastoma is a locally aggressive odontogenic epithelial tumor with poorly understood intraosseous pathogenesis due to a lack of physiologically relevant models. Here, we established an orthotopic intraosseous mouse model using ameloblastoma epithelial cells in combination with ameloblastoma-derived mesenchymal stromal cells (AMMSCs) or their secretome. AMMSC-derived extracellular vesicle-enriched secretome enhances stemness, epithelial-mesenchymal transition (EMT) phenotypes, and tumorigenic ability of ameloblastoma epithelial cells. A unique signature of microRNAs in AMMSC-derived secretome is functionally associated with the upregulation of EMT-regulatory transcription factors in tumor epithelial cells. Single-nucleus ATAC and RNA sequencing revealed a dynamic EMT trajectory in primary human AM-derived epithelial cells activated by paired AMMSC-derived secretome. This study suggests that AMMSCs and their secretome drive orthotopic AM tumor development by promoting tumor epithelial cell proliferation, EMT, and vascular formation in the tumor microenvironment. This stromal-oriented orthotopic model provides a clinically relevant platform for dissecting tumor-stroma crosstalk and identifying therapeutic vulnerabilities in ameloblastoma.
2026-08-09 | GSE317372 | GEO
Project description:RNA-seq analyses of human ameloblastoma and odontogenic keratocyst
| PRJNA774061 | ENA
Project description:Mapping Cellular Senescence in Human Dental Follicle and Odontogenic Keratocyst
| PRJNA1299321 | ENA
Project description:Transformation of odontogenic keratocyst into a solid variant of odontogenic keratocyst/keratoameloblastoma
| PRJDB17197 | ENA