Medulloblastoma (MB) is the most common malignant pediatric brain tumor comprising four main groups characterized by different genetic alterations and rate of mortality. Post-surgery radiotherapy (RT) is actually the standard of care for patients with MB; however, above 40% of patients remains incurable due to treatment failure. Limited treatment efficacy is mainly due to the presence of intrinsically resistant cancer stem cells (CSCs) that survive following comple- tion of standard therapies. Our laboratory recently identified autophagy activation in MB as a strong oncogenic process with translational significance for both patient stratification strategies and for the development of therapies targeting MB CSCs (Nazio et al 2021). Moreover, accumu- lating evidence indicates that autophagy supports metabolic rewiring of cancer cells and that regulators of mitophagy, selective degradation of mitochondria by autophagy, are frequently altered in CSCs. To date, the role of mitochondrial regulatory mechanisms and their effects on the current therapeutic regimen and tumour dissemination in MB remain unknown as well as mitochondrial properties unique to MBSCs need to be defined. Here, we have identified a novel pro-oncogenic role for the poorly studied mitophagy receptor NDP52 as a regulator of MB CSCs malignant phenotype; NDP52 upregulation supports MB CSCs aggressiveness by regulating: i) cell survival, ii) invasion capabilities, iii) mitophagy execution and iv) the response to RT. More- over, we are setting radiotherapy-adapted-(PDX) models of MB recurrence to study how radi- ation-induced changes in MBSCs could affect recurrence and metastasis post-radiotherapy by acting on mitochondria-related mechanisms. Therefore, understanding the molecular mecha- nisms and function of mitophagy in MB during different types of mitochondrial stress and dam- age may be critical for developing the next generation of MB treatment methods

Marabitti, V., Bordi, M., Valle, C., Ferri, A., Cecconi, F., Nazio, F. (2023). Exploring the role of mitophagy in medulloblastoma stem cells dissemination and therapy resistance. ??????? it.cilea.surplus.oa.citation.tipologie.CitationProceedings.prensentedAt ??????? 6th Brainstorming Research Assembly for Young Neuroscientists, Napoli.

Exploring the role of mitophagy in medulloblastoma stem cells dissemination and therapy resistance

Veronica Marabitti
Conceptualization
;
Matteo Bordi
Methodology
;
Francesco Cecconi
Resources
;
Francesca Nazio
Funding Acquisition
2023-09-26

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor comprising four main groups characterized by different genetic alterations and rate of mortality. Post-surgery radiotherapy (RT) is actually the standard of care for patients with MB; however, above 40% of patients remains incurable due to treatment failure. Limited treatment efficacy is mainly due to the presence of intrinsically resistant cancer stem cells (CSCs) that survive following comple- tion of standard therapies. Our laboratory recently identified autophagy activation in MB as a strong oncogenic process with translational significance for both patient stratification strategies and for the development of therapies targeting MB CSCs (Nazio et al 2021). Moreover, accumu- lating evidence indicates that autophagy supports metabolic rewiring of cancer cells and that regulators of mitophagy, selective degradation of mitochondria by autophagy, are frequently altered in CSCs. To date, the role of mitochondrial regulatory mechanisms and their effects on the current therapeutic regimen and tumour dissemination in MB remain unknown as well as mitochondrial properties unique to MBSCs need to be defined. Here, we have identified a novel pro-oncogenic role for the poorly studied mitophagy receptor NDP52 as a regulator of MB CSCs malignant phenotype; NDP52 upregulation supports MB CSCs aggressiveness by regulating: i) cell survival, ii) invasion capabilities, iii) mitophagy execution and iv) the response to RT. More- over, we are setting radiotherapy-adapted-(PDX) models of MB recurrence to study how radi- ation-induced changes in MBSCs could affect recurrence and metastasis post-radiotherapy by acting on mitochondria-related mechanisms. Therefore, understanding the molecular mecha- nisms and function of mitophagy in MB during different types of mitochondrial stress and dam- age may be critical for developing the next generation of MB treatment methods
6th Brainstorming Research Assembly for Young Neuroscientists
Napoli
2023
Rilevanza internazionale
26-set-2023
Settore BIO/06
English
Intervento a convegno
Marabitti, V., Bordi, M., Valle, C., Ferri, A., Cecconi, F., Nazio, F. (2023). Exploring the role of mitophagy in medulloblastoma stem cells dissemination and therapy resistance. ??????? it.cilea.surplus.oa.citation.tipologie.CitationProceedings.prensentedAt ??????? 6th Brainstorming Research Assembly for Young Neuroscientists, Napoli.
Marabitti, V; Bordi, M; Valle, C; Ferri, A; Cecconi, F; Nazio, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/351803
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