Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma

Kondo, Sayuri; Ota, Akinobu; Ono, Takayuki; Karnan, Sivasundaram; Wahiduzzaman, Md; Hyodo, Toshinori; Rahman, Lutfur; Ito, Kunihiro; Furuhashi, Akifumi; Hayashi, Tomio; Konishi, Hiroyuki; Tsuzuki, Shinobu; Hosokawa, Yoshitaka; Kazaoka, Yoshiaki

doi:10.1002/cam4.2931

Cited by 26 publications

(39 citation statements)

References 42 publications

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“…The remarkable similar behavior of CAA genes that are known to be up- and down-regulated in AM 31 demonstrate that canine and human ameloblastomas exhibit a high degree of transcriptional homology. Unsurprisingly, the functional enrichment patterns observed in CAA were comparable to those reported in AM, including notable enrichment of some of the same oncogenic gene sets 31 .…”

Section: Discussionmentioning

confidence: 85%

“…To investigate the extent of molecular homology between CAA and AM, GSEA was performed with custom gene sets derived from previously published sets of genes altered in AM when compared to healthy human gingiva 31 . CAA had significant enrichment of corresponding genes known to be upregulated in AM, with most qualifying as leading-edge including PTHLH , FGFR1 , MMP1 , MMP2 , MMP13 , and COL8A1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…

Figure 6 Homology of CAA with AM and dental identity. Panel ( A ) shows a heat map depicting the relative expression of the top 50% leading-edge genes revealed by custom GSEA testing for enrichment of a set of genes known to be upregulated in AM 31 . The heat map shows clear differences between CAA and control samples, and to a much lesser extent, variation among CAA samples.…”

Section: Resultsmentioning

confidence: 99%

“…We found that the expression profile of CAA is dominated by signatures of aberrant RAS signaling and involves activation of the EMT cellular program. Moreover, CAA exhibits a strong dental identity and is enriched with genes known to be upregulated in AM 31 – 33 . The data suggest a high level of molecular oncogenic program homology of CAA and AM.…”

Section: Discussionmentioning

confidence: 99%

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Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma

Peralta

Duhamel

Katt

et al. 2021

Sci Rep

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Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have clinicopathologic and molecular features in common with human ameloblastomas (AM), spontaneous CAA can serve as a useful translational model of disease. However, the molecular basis of CAA and how it compares to AM are incompletely understood. In this study, we compared the global genomic expression profile of CAA with AM and evaluated its dental origin by using a bulk RNA-seq approach. For these studies, healthy gingiva and canine oral squamous cell carcinoma served as controls. We found that aberrant RAS signaling, and activation of the epithelial-to-mesenchymal transition cellular program are involved in the pathogenesis of CAA, and that CAA is enriched with genes known to be upregulated in AM including those expressed during the early stages of tooth development, suggesting a high level of molecular homology. These results support the model that domestic dogs with spontaneous CAA have potential for pre-clinical assessment of targeted therapeutic modalities against AM.

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Section: Discussionmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

“…

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma

Peralta

Duhamel

Katt

et al. 2021

Sci Rep

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“…Ameloblastoma (AB) is a common epithelial tumor, accounting for more than 60% of odontogenic tumors [1,2]. AB is typically composed of enamel-like structures without any mature enamel or hard tissue being present.…”

Section: Introductionmentioning

confidence: 99%

Wnt5a regulates Ameloblastoma Cell Migration by modulating Mitochondrial and Cytoskeletal Dynamics

Qin¹,

Niu²,

Shi

et al. 2020

J. Cancer

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Objective: Abnormal expression of Wnt5a has been detected in various tumors, including ameloblastoma (AB). Yet, there is no specific mechanistic evidence for the functional role of Wnt5a in AB. In this study, we aimed to conduct a mechanistic examination of the importance of Wnt5a in AB development. Methods: The expressions of Wnt5a and Coro1A were examined by Western blot and immunohistochemistry both in AB tissues and AM-1 cells. The number and size of mitochondria were detected by electronic transmission microscope and confocal microscope. Gain-of-function and loss-of-function assays were used to explore the biological roles of Wnt5a and Coro1A in organelle dynamics changes and cell migration. Cell migration was detected by wound healing and transwell assay. Results: We found that in AM-1 cells, up-regulation of Wnt5a led to enhanced mitochondrial energy production and altered calcium homeostasis, with elevated calcium levels directly leading to altered mitochondrial dynamics and interactions between the cytoskeleton and the mitochondria. When Wnt5a or its downstream cytoskeleton-associated protein Coro1A was knocked down, the migration capacity of AM-1 cells was markedly impaired. Conclusion: Together, these results suggest that Wnt5a plays mitochondria and cytoskeleton specific roles in regulating the development of human AB, with its down-regulation leading to impaired tumor development, thus highlighting Wnt5a or Coro1A as potentially viable therapeutic targets for the treatment of AB.

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Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma

et al. 2023

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BackgroundEpidermal growth factor receptor (EGFR) is frequently overexpressed in oral squamous cell carcinoma (OSCC), and EGFR‐targeting therapeutics have been widely employed to treat patients with a variety of carcinomas including OSCC. Here, we aimed to investigate alternative signaling for OSCC survival under the disruption of EGFR signaling.MethodsOSCC cell lines, namely HSC‐3 and SAS, were utilized to investigate how EGFR disruption affects cell proliferation. Gene set enrichment analysis was performed to examine how EGFR disruption affects oncogenic signaling in OSCC cells. Disruption of KDR gene was performed using CRISPR/Cas9 techniques. A VEGFR inhibitor, vatalanib was used to research the impact of VEGFR inhibition on OSCC survival.ResultsEGFR disruption significantly decreased the proliferation and oncogenic signaling including Myc and PI3K‐Akt, in OSCC cells. Chemical library screening assays revealed that VEGFR inhibitors continued to inhibit the proliferation of EGFR‐deficient OSCC cells. In addition, CRISPR‐mediated disruption of KDR/VEGFR2 retarded OSCC cell proliferation. Furthermore, combined erlotinib–vatalanib treatment exhibited a more potent anti‐proliferative effect on OSCC cells, compared to either monotherapy. The combined therapy effectively suppressed the phosphorylation levels of Akt but not p44/42.ConclusionVEGFR‐mediated signaling would be an alternative signaling pathway for the survival of OSCC cells under the disruption of EGFR signaling. These results highlight the clinical application of VEGFR inhibitors in the development of multi‐molecular‐targeted therapeutics against OSCC.

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Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma

Cited by 26 publications

References 42 publications

Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma

Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma

Wnt5a regulates Ameloblastoma Cell Migration by modulating Mitochondrial and Cytoskeletal Dynamics

Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma

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