Ekspresija članova signalnog puta Hedgehog GLI u primarnim staničnim linijama tumora glave i vrata čovjeka

master's thesis

• Title (english): Expression of Hedgehog GLI signaling pathway members in primary human head and neck tumor cell lines
• Author: Lana Radevenjić
• Mentor: Vesna Musani (mentor)
• Mentor: Domagoj Đikić (komentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Romana Gračan (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Željka Vidaković-Cifrek (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-02-01, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Signalni put Hedgehog-GLI (HH-GLI) je ključan u embrionalnom razvoju čovjeka i drugih sisavaca, a u odraslom organizmu aktivan je samo u održavanju matičnih stanica i cijeljenju rana. Transkripcijski faktori GLI mogu doprinijeti nenormalnoj funkciji ili regulaciji signalizacije što često dovodi do razvoja karcinoma kao što je karcinom pločastih stanica glave i vrata (HNSCC). On obuhvaća tumore koji nastaju u usnoj šupljini, grkljanu, gornjem, srednjem i donjem dijelu ždrijela i žlijezdama slinovnicama te po zastupljenosti predstavlja 6% svih karcinoma u ljudskoj populaciji s izuzetno visokim postotkom smrtnosti. Ovo istraživanje imalo je za cilj proučavanje tumorskih stanica stvaranjem primarnih staničnih linija. Uspoređivali smo gene signalnog puta HH-GLI u tim staničnim linijama s onima u tumorima iz kojih potječu. Također, testirali smo određene inhibitore signalnog puta HH-GLI kako bi se uvidio njihov utjecaj na ekspresiju gena i proteina. Osim toga, usporedili smo dobivene rezultate s onima dobivenim drugim istraživanjem na komercijalnim staničnim linijama. Utvrđeno je da inhibitori, poput LiCl, GANT61 i ATO, različito utječu na signalni put HH-GLI. Konkretno, primijećeno je da LiCl aktivira fosforilaciju GSK3β u citoplazmi, dok GANT61 i ATO, kada se nalaze u jezgri stanice, djeluju izravno na faktore transkripcije. Razumijevanje i manipuliranje tim molekularnim mehanizmima moglo bi utrti put inovativnim terapijskim pristupima u borbi protiv raka povezanih s deregulacijom HH-GLI.

Abstract (english)

The Hedgehog GLI (HH GLI) signaling pathway plays a crucial role in the embryonic
development of humans and other mammals. In the adult organism, its activation is limited to
the stem cells maintenance and wound healing processes. However, dysregulation of GLI
transcription factors in this pathway can lead to aberrant signaling, often contributing to the
development of cancers, such as head and neck squamous cell carcinoma (HNSCC). HNSCC
encompasses tumors arising in various regions, including the oral cavity, larynx, pharynx
(upper, mi ddle, and lower parts), and s alivary glands. It constitutes approximately 6% of all
cancers and is associated with a particularly high mortality rate. This research aimed to study
tumor cells by creating primary cell lines. We compared the HH GLI pathway genes in these
cell lines with those in the tumors they originated from . We also tested certain inhibitors on a
HH GLI pathway to see how they affected expression of genes and proteins. We also compared
our results with another study on commercial cell line s. The inhibitors, like LiCl, GANT61, and
ATO, were found to impact the HH GLI pathway differently. Specifically, LiCl was observed
to activate GSK3 β phosphorylation in the cytoplasm, while GANT61 and ATO, when located
in the cell nucleus , act directly towards influencing transcription factors . Understanding and
manipulating these molecular mechanisms could pave the way for innovative therapeutic
approaches in fighting cancers associated with HH GLI dysregulation.

• Keywords: signalni put HH-GLI; nizvodni inhibitori; primarne stanične linije; tumor pločastih stanica glave i vrata
• Keywords (english): HH GLI signaling pathway; downstream inhibitors; primary cell lines; head and neck squamous cell carcinoma
• Language: croatian
• URN:NBN: urn:nbn:hr:217:554262
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-02-01
• Created on: 2024-04-22 11:47:13