Utjecaj salinomicina na N-glikom u modelu tumorskih matičnih stanica

master's thesis

• Title (english): Effect of salinomycin on N-glycome in a cancer stem cell model
• Author: Filip Kliček
• Mentor: Gordan Lauc (mentor)
• Committee member: Morana Dulić (predsjednik povjerenstva)
• Committee member: Nives Galić (član povjerenstva)
• Committee member: Biserka Prugovečki (član povjerenstva)
• Committee member: Marko Močibob (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2018-12-12, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

N-glikozilacija je post-translacijska modifikacija proteina koja se odvija u endoplazmatskom
retikulumu i Golgijevom aparatu. Modifikacije N-glikana u Golgijevom aparatu su pH ovisne
te je narušavanje homeostaze pH u Golgijevom aparatu vidljivo u promjeni struktura Nglikana.
Efekt salinomicina istraživan je na profilu N-glikana na modelu TMS (HMLE-pBp i
HMLE-Twist). Za salinomicin je prethodno pokazano selektivno djelovanje na tumorske
matične stanice (TMS). Profil N-glikoma sekretiranih proteina se promijenio nakon tretmana
salinomicinom u obje stanične linije. Najuočljivija razlika u profilima nakon tretmana je
izostanak razgranatih kompleksnih glikanskih struktura te relativno povećanje jednostavnih
glikana, što upućuje na to da salinomicin narušava homeostazu u Golgijevom aparatu dok
endoplazmatski retikulum ostaje nepromijenjen. Nadalje, primijetili samo da je efekt
naglašeniji na HMLE-Twist nego na HMLE-pBp staničnoj liniji.

Abstract (english)

N-glycosilation is a post-translational modification of proteins that occurs in endoplasmatic
reticulum and Golgi apparatus. Modifications of N-glycans in the Golgi apparatus are pH
dependent and a disruption of pH homeostasis in Golgi apparatus is visible in the change of
N-glycan structures. We investigated the effect of salinomycin, a cancer stem cell (CSC)
targeting compound, on N-glycan profile of a CSC model (HMLE-pBp and HMLE-Twist cell
lines). N-glycome profile of secreted proteins changed in both cell lines after treatment with
salinomycin. The most evident difference in profiles after treatment is the loss of highly
branched complex glycan structures and the relative increase of simpler glycans, indicating
that salinomycin disrupts the Golgi apparatus homeostasis while the endoplasmatic reticulum
remains intact. Moreover, we noticed that the effect of is more prominent on HMLE-Twist
than on HMLE-pBp cell line.

• Keywords: Golgijev aparat; LC-MS; N-glikozilacija; salinomicin; tumorske matične stanice
• Keywords (english): Golgi apparatus; LC-MS; N-glycosylation; salinomycin; cancer stem cells
• Language: croatian
• URN:NBN: urn:nbn:hr:217:497797
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2020-12-12
• Created on: 2018-12-14 13:18:39