FGF8 induces epithelial-mesenchymal transition and promotes metastasis in oral squamous cell carcinoma

Hao, Yilong; Xiao, Yanxuan; Liao, Xiaoyu; Tang, Shuya; Xie, Xiaoyan; Li, Rui; Chen, Qianming

doi:10.1038/s41368-021-00111-x

Cited by 24 publications

(15 citation statements)

References 43 publications

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“…3 Despite no information is available on FGF8 and OLIG2 in MCC, they are dysregulated in cancer. 15,16 Both genes can be considered as novel candidate MCCPrelated genes.…”

Section: Discussionmentioning

confidence: 99%

Distinct retinoic gene signatures discriminate Merkel cell polyomavirus‐positive from ‐negative Merkel cell carcinoma cells

Mazziotta

Cervellera

Badiale

et al. 2023

Journal of Medical Virology

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Limited molecular knowledge of Merkel cell polyomavirus (MCPyV)-positive and -negative Merkel cell carcinoma (MCC) subsets (MCCP/MCCN) has prevented so far the identification of the MCC origin cell type and, therefore, the development of effective therapies. The retinoic gene signature was investigated in various MCCP, MCCN, and control fibroblast/epithelial cell lines to elucidate the heterogeneous nature of MCC. Hierarchical clustering and principal component analysis indicated that MCCP and MCCN cells were clusterizable from each other and control cells, according to their retinoic gene signature. MCCP versus MCCN differentially expressed genes (n = 43) were identified. Protein-protein interaction network indicated SOX2, ISL1, PAX6, FGF8, ASCL1, OLIG2, SHH, and GLI1 as upregulated hub genes and JAG1 and MYC as downregulated hub genes in MCCP compared to MCCN. Numerous MCCP-associated hub genes were DNA-binding/-transcription factors involved in neurological and Merkel cell development and stemness. Enrichment analyses indicated that MCCP versus MCCN differentially expressed genes predominantly encode for to DNA-binding/-transcription factors involved in development, stemness, invasiveness, and cancer. Our findings suggest the neuroendocrine origin of MCCP, by which neuronal precursor cells could undergo an MCPyV-driven transformation. These overarching results might open the way to novel retinoid-based MCC therapies.

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“…3 Despite no information is available on FGF8 and OLIG2 in MCC, they are dysregulated in cancer. 15,16 Both genes can be considered as novel candidate MCCPrelated genes.…”

Section: Discussionmentioning

confidence: 99%

Distinct retinoic gene signatures discriminate Merkel cell polyomavirus‐positive from ‐negative Merkel cell carcinoma cells

Mazziotta

Cervellera

Badiale

et al. 2023

Journal of Medical Virology

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“…As reported, FGF8 is highly expressed in esophagogastric junction adenocarcinoma, and is expected to be a candidate gene for the prognostic factor for this cancer [ 36 ]. Besides, FGF8 also shows a high expression in oral squamous cell carcinoma tissues, and it regulates the epithelial-mesenchymal transition and induces an invasive phenotype in oral squamous cell carcinoma cells [ 37 ]. Notably, the results of this study also uncovered that miR-6742-5p influenced migration and invasion in LUAD cells by regulating the FGF8 expression, indicating that FGF8 may be a key target for regulating the LUAD progression, and the exogenous FGF8 corrected the roles of miR-6742-5p ( Figure 3C ).…”

Section: Discussionmentioning

confidence: 99%

miR-6742-5p regulates the invasion and migration of lung adenocarcinoma cells via mediating FGF8/ERK12/MMP9/MMP2 signaling pathway

Song

Xing

2023

Aging

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Background: microRNAs (miRNAs) are involved in the progression of Lung adenocarcinoma (LUAD), however, the functions of miR-6742-5p in LUAD remains unknown, thereby this study was carried on. Methods: The mRNA and miRNA expression data from the LUAD and normal control were obtained from Gene Expression Omnibus (GEO) database, TargetScan and mirDIP were applied to predict the relationship between miR-6742-5p and FGF8.Q-PCR, western blot, dual-luciferase, wound Healing and transwell assays were performed to test the functions of miR-6742-5p in LUAD. Results: Bioinformatics analysis and dual-luciferase identified FGF8 is the target-gene of miR-6742-5p, which is declined in LUAD of human tissues and cell lines, and miR-6742-5P OE suppressed the progression of LUAD in nude mice. MiR-6742-5p OE and KD suppressed or increased the abilities of LUAD' metastasis tested by wound healing and transwell assays H522 and PC-9 cells, these effects about miR-6742-5p OE were reversed by FGF8; miR-6742-5p OE, KD inhibited and increased the expression of FGF8 as its downstream p-ERK1/2, MMP-2/-9, these results were corrected by ERK1/2 inhibitor: Ro 67-7476; the miR-6742-5p KD increased the migrated and invaded cells and suppressed by MMPs inhibitor: S3304. These results identified the negative correlation of miR-6742-5p with FGF8-ERK1/2 signal pathway in LUAD progression. Conclusions: We conclude that miR-6742-5p might be a regulator of LUAD progression by targeting FGF8/ERK1/2/MMPs signaling pathway, which provides a novel therapeutic target for LUAD. ETHICAL STATEMENTAll animal experiments were approved by Research Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-R327).

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“… 59 Anomalous FGF8 expression in oral squamous cell carcinoma and hepatoblastoma, instead, promotes metastasis through epithelial-to-mesenchymal transition and modulation of related lineage markers expression. 23 , 56 Moreover, FGF8 induces the expression of PLAU gene in HUVEC cells, 60 that encodes the urokinase-type plasminogen activator (uPA) which plays a major role in tumor progression and metastasis in several cancers, besides in promoting angiogenesis and influencing immune response mechanisms. 61–63 In all these cases, FGF8 acts by linking cell surface receptors and receptor substrates to downstream signal transduction pathways MEK/ERK, PI3K/AKT or STAT/JAK, in a paracrine/autocrine manner that can be prevented by either receptor inhibition, ligand trapping, or neutralizing antibodies treatment.…”

Section: Discussionmentioning

confidence: 99%

Immunoreactivity against fibroblast growth factor 8 in alveolar rhabdomyosarcoma patients and its involvement in tumor aggressiveness

et al. 2022

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Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue sarcoma characterized by a very poor prognosis when relapses occur after front-line therapy. Therefore, a major challenge for patients’ management remains the identification of markers associated with refractory and progressive disease. In this context, cancer autoantibodies are natural markers of disease onset and progression, useful to unveil novel therapeutic targets. Herein, we matched autoantibody profiling of alveolar RMS (ARMS) patients with genes under regulatory control of PAX3-FOXO1 transcription factor and revealed fibroblast growth factor 8 (FGF8) as a novel ARMS tumor antigen of diagnostic, prognostic, and therapeutic potential. We demonstrated that high levels of FGF8 autoantibodies distinguished ARMS patients from healthy subjects and represented an independent prognostic factor of better event-free survival. FGF8 was overexpressed in ARMS tumors compared to other types of pediatric soft tissue sarcomas, acting as a positive regulator of cell signaling. Indeed, FGF8 was capable of stimulating ARMS cells migration and expression of pro-angiogenic and metastasis-related factors, throughout MAPK signaling activation. Of note, FGF8 was found to increase in recurrent tumors, independently of PAX3-FOXO1 expression dynamics. Risk of recurrence correlated positively with FGF8 expression levels at diagnosis and reduced FGF8 autoantibodies titer, almost as if to suggest a failure of the immune response to control tumor growth in recurring patients. This study provides evidence about the crucial role of FGF8 in ARMS and the protective function of natural autoantibodies, giving new insights into ARMS biology and laying the foundations for the development of new therapeutic strategies.

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FGF8 induces epithelial-mesenchymal transition and promotes metastasis in oral squamous cell carcinoma

Cited by 24 publications

References 43 publications

Distinct retinoic gene signatures discriminate Merkel cell polyomavirus‐positive from ‐negative Merkel cell carcinoma cells

Distinct retinoic gene signatures discriminate Merkel cell polyomavirus‐positive from ‐negative Merkel cell carcinoma cells

miR-6742-5p regulates the invasion and migration of lung adenocarcinoma cells via mediating FGF8/ERK12/MMP9/MMP2 signaling pathway

Immunoreactivity against fibroblast growth factor 8 in alveolar rhabdomyosarcoma patients and its involvement in tumor aggressiveness

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