Unit:
Κατεύθυνση Εφαρμογές της Βιολογίας στην ΙατρικήLibrary of the School of Science
Author:
Malakou Stavroula-Nikoletta
Supervisors info:
Αναπληρώτρια Καθηγήτρια Μαρία Γαζούλη (Επιβλέπουσα),
Εργαστήριο Βιολογίας, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Καθηγητής Ευάγγελος Μαρίνος,
Εργαστήριο Βιολογίας, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Αναπληρωτής Καθηγητής Δημήτριος Ι. Στραβοπόδης,
Τομέας Βιολογίας Κυττάρου και Βιοφυσικής, Βιολογικό Τμήμα, Σχολή Θετικών Επιστημών Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
«Συσχέτιση των μηχανοευαίσθητων πολυκυστινών και φλεγμονωδών παραγόντων στην παθογένεια του ορθοκολικού καρκίνου»
Translated title:
The role of mechanosensitive polycystins and inflammatory agents in the pathogenesis of colorectal cancer"
Summary:
Polycystins 1 and 2 (PC1, PC2) are proteins that are expressed in many types of epithelial cells, contributing to the pathogenesis of autosomal dominant polycystic kidney disease. They function as motor ‐ sensing molecules that regulate cellular response and play a homeostatic role in key cellular functions that are disturbed during oncogenesis, potentially assuming their biological involvement mainly in the processes of tumor expansion and metastasis. They also appear to play a key role in colon cancer, autoimmune dominant polycystic kidney disease and psoriasis. The common feature of these 3 diseases is the close pathogenetic association with inflammatory mechanisms.
Colorectal cancer is one of the most important multifactorial cancers. The development of inflammation in the colon environment plays a key role in its development.
The aim of the master's thesis was to investigate for the first time the role of polycystins in inflammation during carcinogenesis using a model of colorectal cancer (CRC) as a model, which is a common malignancy in both sexes that is well thought out and hierarchically structured.
Hypoexpression of Polycystin-1 promotes activation of molecules such as mTOR, with subsequent expression of VEGF, which is a key factor in inflammation. Also, transcriptional silencing of Polycystin 1, leads to accumulation of IKKβ in the cytoplasm and increased activation of NF-Kb, which then regulates the expression of inflammatory-related genes. STAT3, which also activates several cytokine genes, is affected by Polycystin-1 hypoexpression and exhibits elevated levels of activation.
Finally, inflammatory environment in colorectal cancer affects the expression of Polycystin-1, with pro-inflammatory cytokines causing a decrease in its expression.
In conclusion, Polycystin-1 may be a novel effector of inflammation, involved in pathological mechanisms of development of an aggressive phenotype in colorectal cancer, and may be a new therapeutic targeting molecule.
Main subject category:
Science
Keywords:
polycystin‐1,colorectal cancer, carcinogenesis, inflammation, mTOR, VEGF, NF-Kb, STAT3
Number of references:
116
