Molecular biological findings of ameloblastoma

Fuchigami, Takao; Ono, Yoshio; Kishida, Shosei; Nakamura, Norifumi

doi:10.1016/j.jdsr.2020.12.003

Cited by 23 publications

(21 citation statements)

References 85 publications

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“…However, AMs can also demonstrate local invasive growth and aggressive behavior characterized by marked bone destruction and a high recurrence rate. Increasing evidence has revealed that tumor driver genes or tumor suppressors play important roles in the development and progression of AM ( 1 , 2 , 18 ). Importantly, the BRAF V600 mutation has been confirmed to be the most common and critical oncogenic mutation in AM, and it leads to a continuous overactivation of mitogen-activated protein kinase (MAPK) signaling and its target genes ( 2 , 19 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…Ameloblastoma (AM) is a locally aggressive benign odontogenic epithelial tumor that usually occurs in the jawbone and arises from the dental lamina, epithelial rests of Malassez, or the basal cell layer of the oral epithelium ( 1 , 2 ). In 2017, the WHO’s new classification of AM was simplified and made more practical, and it reserved two subtypes (unicystic type and extraosseous/peripheral type) and referred to the remaining types as AMs (conventional) ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

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FOSL1 promotes tumor growth and invasion in ameloblastoma

et al. 2022

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BackgroundFOSL1, a key component of the Activating protein-1 (AP-1) transcriptional complex, plays an important role in cancer cell migration, invasion, and proliferation. However, the impact of FOSL1 in ameloblastoma (AM) has not been clarified. Herein, we aimed to assess the expression of FOSL1 and investigate its functional role in AM.MethodsThe expression of FOSL1 was examined based on an immunohistochemistry analysis of 96 AM samples. Cell proliferation, migration, invasion, and tumorigenesis were assessed using Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and sphere formation assays. RNA sequencing (RNA-seq) was employed to investigate the molecular alterations of AM cells upon FOSL depletion. Microarrays of AMs were downloaded from the Gene Expression Omnibus (GEO) database for bioinformatics analysis. In addition, patient-derived AM organoids were used to evaluate the therapeutic value of the AP-1 inhibitor.ResultsFOSL1 was detected in the nuclei of AMs and upregulated in conventional AMs compared to unicystic AMs and normal oral epithelium. Compared with primary AM, FOSL1 expression was significantly increased in recurrent AM. Genetic knockdown of FOSL1 suppressed the proliferation, migration, invasion, and sphere formation of AMs. Similar results were also observed by pharmacological inhibition of AP-1 activity. Moreover, the AP-1 inhibitor T5224 impeded the growth of organoids derived from AM patients. Mechanistically, our Ingenuity Pathway Analysis (IPA) and gene set enrichment analysis (GSEA) results revealed that depletion of FOSL1 inactivated kinetochore metaphase signaling and the epithelial–mesenchymal transition pathway and then impaired the aggressiveness of AM cells accordingly.ConclusionFOSL1 promotes tumor recurrence and invasive growth in AM by modulating kinetochore metaphase signaling and the epithelial–mesenchymal transition pathway; thus, it represents a promising therapeutic target for AM treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FOSL1 promotes tumor growth and invasion in ameloblastoma

et al. 2022

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“…There is evidence to indicate that tumor cells secrete factors related to bone resorption and invasion, such as MMPs and receptor activator nuclear factor kappa B ligand (RANKL), and interact with surrounding stromal components to construct a microenvironment favorable for tumor growth in ameloblastoma [54]. In addition, there is reduced activation of immune reaction in the ameloblastoma tumor microenvironment.…”

Section: Recent Advancesmentioning

confidence: 99%

Ameloblastoma: An Updated Narrative Review of an Enigmatic Tumor

Ghai¹

2022

Cureus

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Ameloblastoma is one of the most common benign odontogenic tumors of the jaw that constitutes about 10% of all tumors that arise in the mandible and maxilla. It is a slow-growing but locally invasive tumor that presents with painless swelling of the mandible or maxilla. The World Health Organization (WHO) classification of 2017 describes ameloblastomas of the following four types: ameloblastoma; unicystic ameloblastoma; extraosseous/peripheral ameloblastoma; and metastasizing ameloblastoma. The diagnosis of ameloblastoma requires computerized tomography (CT) imaging as well as a biopsy. A biopsy is helpful in differentiating ameloblastoma from ossifying fibroma, osteomyelitis, giant cell tumor, cystic fibrous dysplasia, myeloma, and sarcoma. The best treatment of ameloblastoma is aggressive en bloc resection with simultaneous reconstruction. The high recurrence rate and large tissue defects have been long-standing issues in the treatment of ameloblastoma. Recent molecular developments strongly suggest the possibility of targeted therapy with better outcomes in ameloblastomas. We present a detailed updated narrative review of our current understanding and management of this enigmatic tumor.

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“…Ameloblastoma (AM) is a typical benign odontogenic tumor, accounting for 59.3% ~ 63.2% of odontogenic tumors [1][2][3]. It is common in the jaw, 80% of which occurs in the mandible [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

A Modified Surgical Approach for the Treatment of Classic Ameloblastoma in Young Patients

Zhang¹,

Chen²,

Zhang³

2022

J Clin Med Res

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Objective — To analyze the clinical efficacy and application characteristics of the sequence method in the treatment of young patients with large cystic classic ameloblastoma (AM). Methods — 16 young patients with large cystic classic AM treated in the Department of Stomatology of the First Affiliated Hospital of Bengbu Medical College from February 2012 to August 2019 were selected. According to the patient's age, imaging examination, and pathological diagnosis, the sequence method was used for treatment. The patients were followed up regularly after the operation. Results — The patients were followed up for more than 2 years. Of the 16 patients, 13 had no recurrence after fenestration + first curettage, 3 had recurrence after fenestration + first curettage, and 2 had no recurrence after secondary curettage. One patient recurred after repeated curettage and followed up for 10 years and underwent osteotomy. Conclusion — Sequence method can play a good therapeutic effect on young large cystic classic AM.

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Molecular biological findings of ameloblastoma

Cited by 23 publications

References 85 publications

FOSL1 promotes tumor growth and invasion in ameloblastoma

FOSL1 promotes tumor growth and invasion in ameloblastoma

Ameloblastoma: An Updated Narrative Review of an Enigmatic Tumor

A Modified Surgical Approach for the Treatment of Classic Ameloblastoma in Young Patients

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