Ruiter, Nikee (2026) Characterizing the Role of CHMP6 in the Inflammatory Response of Cells within Chromosomal Instability. Master's Research Project 2, Biomolecular Sciences.
|
Text
mMBB2026RuiterN.pdf Download (1MB) | Preview |
Abstract
Chromosomal instability (CIN) is a hallmark of cancer and is associated with chronic acƟvaƟon of inflammatory signaling pathways, including the cGAS-STING-interferon axis. While interferon signaling can promote anƟ-tumor immunity, sustained acƟvaƟon poses a survival challenge for CIN-posiƟve cancer cells, suggesƟng the existence of regulatory mechanisms that buffer the inflammatory stress. In this study, the role of Charged MulƟvesicular Body Protein 6 (CHMP6), a core component of the ESCRTIII complex, was invesƟgated in the context of CIN-associated inflammatory signaling. Using an ISRE-GFP-iCasp9 reporter system, interferon pathway acƟvaƟon was validated in response to IFNß treatment and CIN inducƟon. A prior CRISPR screen idenƟfied CHMP6 as a candidate regulator of interferon signaling. siRNA-mediated depleƟon of CHMP6 in mulƟple cell lines resulted in increased reporter acƟvity and upregulaƟon of interferon-sƟmulated genes, indicaƟng acƟvaƟon of inflammatory signaling in a cell-line dependent manner. CHMP6 knockdown also led to reduced LaminB1 mRNA expression, suggesƟng compromised nuclear envelope integrity. While alteraƟons in total STING levels were observed, phosphorylated STING and cGAS foci could not be conclusively detected. Together, these findings support a model in which CHMP6 funcƟons as a negaƟve regulator of inflammatory signaling in CIN-posiƟve cells, potenƟally by maintaining membrane integrity and limiƟng chronic interferon pathway acƟvaƟon. This study established CHMP6 as a buffering factor in CINassociated inflammatory responses and provides a foundaƟon for future invesƟgaƟon into its role in cell fate regulaƟon.
| Item Type: | Thesis (Master's Research Project 2) |
|---|---|
| Supervisor name: | Foijer, F. |
| Degree programme: | Biomolecular Sciences |
| Thesis type: | Master's Research Project 2 |
| Language: | English |
| Date Deposited: | 01 Apr 2026 09:03 |
| Last Modified: | 01 Apr 2026 09:03 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/37275 |
Actions (login required)
 |
View Item |