FOSL1 promotes tumor growth and invasion in ameloblastoma

Abstract

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.

Overexpression of zinc finger DHHC-type containing 1 is associated with poor prognosis and cancer cell growth and metastasis in uterine corpus endometrial carcinoma

“…Tumor development involves multiple signaling mechanisms [ 14 , 15 ], and GSEA is a commonly used method to investigate the signaling mechanisms of individual or many genes involved in cancer progression [ 11 , 16 ]. The ZDHHC1 gene was subjected to GSEA on the UCEC data from the TCGA database using the CAMOIP software.…”

Notch-signaling is required for mediating between two pattern forming processes during head regeneration inHydrapolyps

“…This is similar to human cFos, which does not form homodimers, but heterodimerises with Jun-proteins (Kouzarides and Ziff 1988). Assuming that HyKayak may be forming dimers with HyJun_epi we used the Fos/jun-inhibitor T5224 to block DNA-binding of Fos/Jun-complexes (Xiong, Ouyang et al 2022) and analyzed resulting gene expression and phenotypes during Hydra head regeneration. This revealed a slight inhibition of HyKayak expression in contrast to strong up-regulation of HyJun (Fig.…”