Remodeliranje aktinskog citoskeleta i bijeg stanica raka od imunosnog nadzora

undergraduate thesis

• Title (english): Actin cytoskeleton remodeling and immune evasion of cancer cells
• Author: Lana Semenić
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Ovaj rad istražuje mehanobiologiju raka i imunosnog sustava, pritom razmatrajući remodeliranje
aktinskog citoskeleta kao potencijalnu strategiju imunosnog bijega. Poput koncepta imunosnog nadzora,
koji je danas široko prihvaćen, uloga fizikalnih svojstava tumorskih stanica u progresiji raka isprva je
naišla na kontroverze. Međutim, otkriće pozitivne korelacije između krutosti izvanstaničnog matriksa i
tumorskog fenotipa dugotrajno je obilježilo mehanobiologiju raka kao obećavajuće područje
istraživanja. S vremenom, interes istraživača proširio se na čimbenike stanične krutosti i njihov značaj
u imunosnoj sinapsi. Stanicama raka se tijekom metastatske kaskade mijenjaju morfologija i elastična
svojstva, za što je velikim dijelom zaslužna dinamičnost aktinskog citoskeleta. Tijekom prostiranja po
perivaskularnoj niši, dolazi do pojačanja signalizacije transkripcijskim čimbenikom povezanim s
miokardinom (MRTF). Ona povećava broj aktinskih filamenata u stanici, čija organizicija u stresna
vlakna povećava staničnu krutost. Ovo ih čini prepoznatljivijima za limfocite i time podložnijima
eliminaciji. Budući da se radi o nužnom koraku metastatske kaskade, stanice raka moraju precizno
regulirati ovu signalizaciju kako bi ostvarile imunosni bijeg te formirale metastatsku koloniju. Kao drugi
potencijalni mehanizam bijega predstavio se aktinski odgovor tumorske stanice, ali su mu detalji ostali
nepoznati.

Abstract (english)

This thesis explores cancer and immune system mechanobiology, while considering actin cytoskeleton
remodeling as a potential immune evasion strategy. Similarly to the now widely accepted concept of
immunosurveillance, the role of cellular mechanical properties in cancer progression ran into
controversy at first. However, the discovery of a positive correlation between extracellular matrix
stiffness and tumor phenotype has lastingly marked cancer mechanobiology as a promising field of
study. Over time, researchers' interest has encompassed cell stiffness determining factors and their
significance in immune synapse. During metastatic cascade, cancer cells undergo changes in
morphology and elastic properties. This is primarily caused by actin cytoskeleton dynamics. Spreading
of cancer cells across the perivascular niche is characterized by an increase in myocardin-related
transcription factor (MRTF) signaling. This increases the amount of cellular actin filaments, which then
assemble into stress fibers, thus increasing cellular stiffness. The increase in stiffness makes cells more
stimulatory to lymphocytes and therefore more susceptible to elimination. Since the afforementioned
step is crucial in the metastatic cascade, cancer cells need to finely regulate MRTF signaling in order to
successfully avoid elimination and form colonies. Tumor cell actin response has been suggested as an
alternative evasion mechanism, however its details remain elusive.

• Keywords: imunosna sinapsa; mehanobiologija; mehanonadzor; metastaza
• Keywords (english): : immune synapse; mechanobiology; mechanosurveillance; metastasis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:500847
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-10-13 10:37:53