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%2F67985904%3A_____%2F22%3A00559671" target="_blank" >RIV/67985904:_____/22:00559671 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00843989:_____/22:E0109656 RIV/00216224:14310/22:00129706 RIV/61988987:17110/22:A2302ITU RIV/62157124:16170/22:43880046

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S000399692200156X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S000399692200156X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.archoralbio.2022.105499" target="_blank" >10.1016/j.archoralbio.2022.105499</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alteration of primary cilia morphology and associated signalling in ameloblastoma

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Alteration of primary cilia morphology and associated signalling in ameloblastoma

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30208 - Dentistry, oral surgery and medicine

Projekt

<a href="/cs/project/NU20-08-00205" target="_blank" >NU20-08-00205: Molekulární etiopatogeneze apikální periodontitidy a odontogenních cyst</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Archives of Oral Biology

ISSN

0003-9969

e-ISSN

1879-1506

Svazek periodika

142

Číslo periodika v rámci svazku

OCT 2022

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

105499

Kód UT WoS článku

000831041300002

EID výsledku v databázi Scopus

2-s2.0-85134517605