J 2022

Alteration of primary cilia morphology and associated signalling in ameloblastoma

FILUŠOVÁ, Jana, Iveta PUTNOVA, Pavel HURNÍK, Zdeněk DANĚK, Ctirad MACHÁČEK et. al.

Basic information

Original name

Alteration of primary cilia morphology and associated signalling in ameloblastoma

Authors

FILUŠOVÁ, Jana (703 Slovakia), Iveta PUTNOVA (203 Czech Republic, guarantor), Pavel HURNÍK (203 Czech Republic, belonging to the institution), Zdeněk DANĚK (203 Czech Republic, belonging to the institution), Ctirad MACHÁČEK (203 Czech Republic, belonging to the institution), Jan ŠTEMBÍREK (203 Czech Republic), Marcela BUCHTOVÁ (203 Czech Republic, belonging to the institution) and Barbora PUTNOVA MOLDOVAN (203 Czech Republic)

Edition

Archives of Oral Biology, Amsterdam, Elsevier, 2022, 0003-9969

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30208 Dentistry, oral surgery and medicine

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.000

RIV identification code

RIV/00216224:14310/22:00129706

Organization unit

Faculty of Science

UT WoS

000831041300002

Keywords in English

Ameloblastoma; SHH; IFT; Primary cilia

Tags

International impact, Reviewed
Změněno: 13/3/2023 08:02, Mgr. Marie Šípková, DiS.

Abstract

V originále

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.

Links

NU20-08-00205, research and development project
Name: Molekulární etiopatogeneze apikální periodontitidy a odontogenních cyst
Investor: Ministry of Health of the CR, Subprogram 1 - standard