Alteration of primary cilia morphology and associated signalling in ameloblastoma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16170%2F22%3A43880122" target="_blank" >RIV/62157124:16170/22:43880122 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Alteration of primary cilia morphology and associated signalling in ameloblastoma

Popis výsledku v původním jazyce

Primary cilia are microtubular organelles, central to several pathways of cellular signalling. As such, they have been confirmed to play a significant role in tumour biology, which makes them interesting from a scientific standpoint. In our research, we have investigated the occurrence, morphology, and associated gene expression of primary cilia in ameloblastoma, which is the most common tumour of odontogenic origin. Moreover, we compared our findings from ameloblastoma to oral squamous cell carcinoma. Our results indicate differences in cilia distribution and appearance among three histological subtypes of ameloblastoma (basocellular, plexiform and follicular), with plexiform and follicular subtypes having elevated cilia counts in comparison to control tissue. These subtypes also exhibit altered cilia shape and length. In contrast, oral squamous cell carcinoma cells are almost entirely lacking cilia. The association of Sonic Hedgehog (SHH) signalling and primary cilia is very well known, therefore we analysed gene expression of key members of this pathway. SHH receptor PTCH1 and the downstream transcription factor GLI1 were upregulated in all ameloblastoma subtypes. Inhibition of Hedgehog signalling by LDE255 (SMO inhibitor) led to downregulation of GLI1 and CCND1 expression in cell cultures, while leading both to upregulation of IFT20 and downregulation of IFT88 genes. These findings implicate the enhanced Hedgehog signalling activity in ameloblastoma, which correlated with alterations in cilia numbers. SHH inhibitors could thus be considered as a potential therapeutic target for ameloblastoma treatment

Název v anglickém jazyce

Alteration of primary cilia morphology and associated signalling in ameloblastoma

Popis výsledku anglicky

Primary cilia are microtubular organelles, central to several pathways of cellular signalling. As such, they have been confirmed to play a significant role in tumour biology, which makes them interesting from a scientific standpoint. In our research, we have investigated the occurrence, morphology, and associated gene expression of primary cilia in ameloblastoma, which is the most common tumour of odontogenic origin. Moreover, we compared our findings from ameloblastoma to oral squamous cell carcinoma. Our results indicate differences in cilia distribution and appearance among three histological subtypes of ameloblastoma (basocellular, plexiform and follicular), with plexiform and follicular subtypes having elevated cilia counts in comparison to control tissue. These subtypes also exhibit altered cilia shape and length. In contrast, oral squamous cell carcinoma cells are almost entirely lacking cilia. The association of Sonic Hedgehog (SHH) signalling and primary cilia is very well known, therefore we analysed gene expression of key members of this pathway. SHH receptor PTCH1 and the downstream transcription factor GLI1 were upregulated in all ameloblastoma subtypes. Inhibition of Hedgehog signalling by LDE255 (SMO inhibitor) led to downregulation of GLI1 and CCND1 expression in cell cultures, while leading both to upregulation of IFT20 and downregulation of IFT88 genes. These findings implicate the enhanced Hedgehog signalling activity in ameloblastoma, which correlated with alterations in cilia numbers. SHH inhibitors could thus be considered as a potential therapeutic target for ameloblastoma treatment

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

40301 - Veterinary science

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů