Uloga proteina Kank1 i Kank2 u osjetljivosti stanica melanoma RPMI-7951 na paklitaksel

master's thesis

• Title (english): The role of Kank1 and Kank2 proteins in sensitivity of melanoma cells RPMI-7951 to paclitaxel
• Author: Marta Acman
• Mentor: Andreja Ambriović Ristov (mentor)
• Committee member: Kristina Radošević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Biology and Microbial Genetics); Zagreb
• Defense date and country: 2021-03-08, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Integrini, receptori za izvanstanični matriks, tvore multimolekularne komplekse koji povezuju izvanstanični matriks i aktinski citoskelet te koji se posredstvom Kank proteina povezuju s mikrotubulima. Integrini αV, posebice αVβ3 i αVβ5, uključeni su u rast tumora, angiogenezu i metastaziranje i oba su povezana sa lošim prognozama u melanomu. Naša dosadašnja istraživanja su pokazala da utišavanje integrina αV povećava osjetljivost stanica melanoma, MDA-MB-435S i RPMI- 7951, na protutumorski lijek paklitaksel koji djeluje putem mikrotubula. Analizom adhesoma otkriveno je da ove stanice preferencijalno koriste integrin αVβ5 te je, uz brojne druge proteine, otkrivena prisutnost proteina Kank1 i Kank2 u MDA-MB-435S odnosno Kank2 u RPMI-7951 adhesomu. Utišavanje Kank2 u stanicama MDA-MB-435S imitira učinak utišavanja integrina αV i povećava osjetljivost na paklitaksel. Cilj ovog istraživanja bio je utvrditi ulogu proteina Kank1 i 2 u osjetljivosti stanica RPMI-7951 na paklitaksel. Pokazano je da stanice RPMI-7951 eksprimiraju oba Kank proteina te da utišavanje Kank1 i/ili 2 nema ulogu u osjetljivosti stanica RPMI-7951 na paklitaksel ukazujući na različite mehanizme povećanja osjetljivosti nakon utišavanja integrina αV u stanicama melanoma.

Abstract (english)

Integrins are receptors for extracellular matrix that form multimolecullar integrin adhesion complexes thus connecting extracellular matrix and actin cytoskeleton. These integrin adhesion complexes connect with microtubules through Kank proteins. αV integrins, in particular αVβ3 and αVβ5, are known to be involved in tumor growth, angiogenesis and formation of metastases, and have both been associated with poor prognosis in melanoma. Our previous studies have shown that integrin aV knockdown enhances sensitivity of MDA-MB-435S and RPMI-7951 melanoma cells to antitumor drug paclitaxel. Adhesome analyses have shown that these cell lines preferentially use integrin αVβ5 for adhesion. Among others, Kank1 and Kank2 proteins have been identified in MDA-MB-435S and Kank2 in RPMI-7951 integrin adhesion complexes. Knockdown of Kank2 in MDA-MB-435S cells mimics the effect of integrin aV knockdown and enhances sensitivity to paclitaxel. The goal of this research was to define the role of Kank1 and 2 in sensitivity of RPMI-7951 melanoma cells to paclitaxel. Here, we demonstrate that RPMI-7951 cells express both Kank1 and Kank2 proteins and that knockdown of any or both does not affect the sensitivity of RPMI-7951 to paclitaxel thus pointing to different mechanisms of sensitisation of melanoma cells to paclitaxel upon integrin αV knockdown.

• Keywords: melanom; adhesom; integrin αV; paklitaksel; Kank proteini
• Keywords (english): melanoma; cell adhesion; integrin αV; paclitaxel; Kank proteins
• Language: croatian
• URN:NBN: urn:nbn:hr:159:082828
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-03-17 10:30:36