Alteration of primary cilia morphology and associated signalling in ameloblastoma

Objectives: Primary cilium is a cellular organelle with growing significance confirmed in tumour biology. Primary cilia have been associated with fine tuning of numerous cell signalling pathways and the role of this structure in cancer initiation and progression is recently at the forefront of attention. Here, we investigated possible alter-ations in the occurrence of primary cilia and changes of associated signalling in ameloblastoma, which represents the most common odontogenic tumour. Methods: We performed immunohistochemistry to assess the number and morphology of primary cilia in ame-loblastoma tissues. The gene expression of key SHH pathway members was analysed by qPCR. As a functional experiment, we treated a primary ameloblastoma cell line by a SHH pathway inhibitor Sonidegib (LDE225). Results: We uncovered differences in primary cilia distribution and appearance in histological subtypes of ameloblastoma with the highest number of ciliated cells in plexiform and follicular subtypes. SHH protein was located close to primary cilia in ameloblastoma epithelial cells and the expression of molecules downstream of SHH signalling was upregulated. Moreover, the inhibition of SHH pathway by Sonidegib caused downregulation of SHH effector gene GLI1 and cell cycle regulator CCND1 in ameloblastoma primary cell line. The inhibition of SHH signalling also altered the expression of molecules involved in intraflagellar transport. Conclusions: In conclusion, our study uncovered alterations in number of ciliated cells and associated signalling in ameloblastoma, which indicate SHH inhibitors as potential therapeutic target to treat this disease.

Automated summary

This study investigated alterations in the occurrence of primary cilia and associated signaling in ameloblastoma, a common odontogenic tumor. The study found differences in the distribution and appearance of primary cilia among histological subtypes of ameloblastoma. The expression of molecules downstream of the SHH signaling pathway was upregulated, and inhibition of the pathway led to downregulation of SHH effector genes and cell cycle regulators. These findings suggest that SHH inhibitors could be a potential therapeutic target for treating ameloblastoma.