Micronuclei are small nucleus-like bodies located in the cytoplasm, that are separated from the primary nucleus of the cell and are surrounded by their proper membrane. Since their origin resides in errors during DNA replication, DNA repair and chromosome missegregation during mitosis, they are considered as markers of chromosomal instability (CIN). However, recent discoveries point out that micronuclei play an active role in several biological processes, such as senescence, inflammation, cell death, cancer, and particularly metastasis. For this reason, dissecting the molecular features characterizing micronuclei is fundamental for research. In detail, this thesis will focus on the cGAS-STING axis: a signalling pathway that is involved in micronuclei homeostasis and can confer controversial roles to micronuclei in a context-dependent manner, according to the level of CIN. This study will provide some criteria to better understand the relevance of micronuclei in different cellular contexts, focusing particularly on the role of cGAS-STING pathway in Triple Negative Breast Cancer cells and hypothesizing novel possible therapeutic interventions for cancer patients.

I micronuclei e il pathway di cGAS-STING: recenti scoperte e future applicazioni per il trattamento del cancro

ZELONI, ROBERTA
2021/2022

Abstract

Micronuclei are small nucleus-like bodies located in the cytoplasm, that are separated from the primary nucleus of the cell and are surrounded by their proper membrane. Since their origin resides in errors during DNA replication, DNA repair and chromosome missegregation during mitosis, they are considered as markers of chromosomal instability (CIN). However, recent discoveries point out that micronuclei play an active role in several biological processes, such as senescence, inflammation, cell death, cancer, and particularly metastasis. For this reason, dissecting the molecular features characterizing micronuclei is fundamental for research. In detail, this thesis will focus on the cGAS-STING axis: a signalling pathway that is involved in micronuclei homeostasis and can confer controversial roles to micronuclei in a context-dependent manner, according to the level of CIN. This study will provide some criteria to better understand the relevance of micronuclei in different cellular contexts, focusing particularly on the role of cGAS-STING pathway in Triple Negative Breast Cancer cells and hypothesizing novel possible therapeutic interventions for cancer patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14240/85118