Utjecaj izmjene E- i N-kadherina na fosforilacijski status beta-katenina i epitelno-mezenhimsku tranziciju u intrakranijalnim meningeomima

doctoral thesis

• Title (english): The impact of E- and N-cadherin switch on phosphorylation status of beta-catenin and the epithelial-mesenchymal transition in intracranial meningiomas
• Author: Anja Bukovac
• Mentor: Nives Pećina-Šlaus (mentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Epitelno-mezenhimska tranzicija (EMT) koju karakterizira kadherinska izmjena, odnosno smanjena ekspresija E-kadherina, a pojačana N-kadherina, ima važnu ulogu u mehanizmima invazivnosti i metastaziranja tumorskih stanica. Klasični signalni put Wnt usko je povezan s procesima EMT, te je poznato da prijelaz β-katenina u jezgru može dovesti do EMT. U ovom istraživanju pokazano je da geni sudionici kadherinske izmjene, CDH1 i CDH2 imaju ulogu u progresiji meningeoma te je zabilježena viša ekspresija N-kadherina u odnosu na E-kadherin. Ekspresija transkripcijskih faktora SNAIL, SLUG i TWIST1 u meningeomima bila je izrazito jača od E- i N-kadherina, a SNAIL i SLUG su bili značajno povezani s višim gradusima (p=0,001) ukazujući na njihovu ulogu u progresiji. Viši gradusi bilježe i porast ekspresije ukupnog β-katenina koju prati i porast ekspresije njegovog aktivnog oblika (p=0,000). Istraživanje ove disertacije donosi prve rezultate genetičkih i proteinskih analiza važnih molekula signalnog puta Wnt i EMT te otkiva njihovu ulogu u intrakranijalnim meningeomima. Također, rezultati istraživanja nude smjernice i nove biljege progresije za buduća istraživanja te otkrivaju nove molekularne mete terapeutskih intervencija.

Abstract (english)

Epithelial to mesenchymal transition (EMT), which is characterized by reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes involved in cadherin switch, CDH1 and CDH2, play a role in meningioma progression. Also, increased expression of N-cadherin in relation to E-cadherin was recorded. In meningiomas, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-kadherin. Expression of SNAIL and SLUG was significantly associated with higher grades (p=0,001) indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form (p=0,000). This dissertation research brings the first results of genetic and protein analyzes of important molecules involved in WNT and EMT signaling pathways and reveals their role in intracranial meningiomas. Results of this research offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions.

• Keywords: intrakranijalni meningeomi; epitelno-mezenhimska tranzicija; signalni put Wnt; E-kadherin; N-kadherin; β-katenin
• Keywords (english): intracranial meningioma; epithelial-mesenchymal transition; Wnt signaling pathway; E-cadherin; N-cadherin; β-catenin
• Language: croatian
• URN:NBN: urn:nbn:hr:217:459234
• Promotion: 2021
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-10-30
• Created on: 2021-01-29 12:30:26