The unfolded protein response in glioblastoma stem cells: towards new targets for therapy

Natalia Peñaranda Fajardo

doi:10.33612/diss.118411504

The unfolded protein response in glioblastoma stem cells: towards new targets for therapy

Natalia Peñaranda Fajardo

Research output: Thesis › Thesis fully internal (DIV)

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Abstract

The aim of this thesis was to investigate ER stress/ UPR signalling in GSCs and explore its potential as a target for therapy in GBM. The importance of the UPR in contributing to acute ER stress-induced cytotoxicity was examined, including effects on the self-renewal potential of GSCs and the underlying molecular mechanisms were elucidated. For this, previously in our lab generated and characterized patient-derived GSC-enriched GBM neurosphere models were employed. A novel noncanonical mechanism for PERK was identified that regulates differentiation and stemness in GSCs. We conclude that ER stress-inducing therapies and PERK modulation may provide promising therapeutic approaches in GBM.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	University of Groningen
Supervisors/Advisors	Kruyt, Frank, Supervisor Meijer, Coby, Co-supervisor
Award date	11-May-2020
Place of Publication	[Groningen]
Publisher	Rijksuniversiteit Groningen
Print ISBNs	978-94-034-2469-9
Electronic ISBNs	978-94-034-2470-5
DOIs	https://doi.org/10.33612/diss.118411504
Publication status	Published - 2020

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10.33612/diss.118411504

Title and contentsFinal publisher's version, 194 KB
Chapter 1Final publisher's version, 245 KB
Chapter 2Final publisher's version, 734 KB
Chapter 3Final publisher's version, 15.1 MB
Chapter 4Final publisher's version, 2.1 MB
Chapter 5Final publisher's version, 14 MB
Chapter 6Final publisher's version, 476 KB
AppendicesFinal publisher's version, 382 KB
Complete thesisFinal publisher's version, 30 MB
PropositionsFinal publisher's version, 106 KB

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title = "The unfolded protein response in glioblastoma stem cells: towards new targets for therapy",

abstract = "The aim of this thesis was to investigate ER stress/ UPR signalling in GSCs and explore its potential as a target for therapy in GBM. The importance of the UPR in contributing to acute ER stress-induced cytotoxicity was examined, including effects on the self-renewal potential of GSCs and the underlying molecular mechanisms were elucidated. For this, previously in our lab generated and characterized patient-derived GSC-enriched GBM neurosphere models were employed. A novel noncanonical mechanism for PERK was identified that regulates differentiation and stemness in GSCs. We conclude that ER stress-inducing therapies and PERK modulation may provide promising therapeutic approaches in GBM.",

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AU - Peñaranda Fajardo, Natalia

PY - 2020

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N2 - The aim of this thesis was to investigate ER stress/ UPR signalling in GSCs and explore its potential as a target for therapy in GBM. The importance of the UPR in contributing to acute ER stress-induced cytotoxicity was examined, including effects on the self-renewal potential of GSCs and the underlying molecular mechanisms were elucidated. For this, previously in our lab generated and characterized patient-derived GSC-enriched GBM neurosphere models were employed. A novel noncanonical mechanism for PERK was identified that regulates differentiation and stemness in GSCs. We conclude that ER stress-inducing therapies and PERK modulation may provide promising therapeutic approaches in GBM.

AB - The aim of this thesis was to investigate ER stress/ UPR signalling in GSCs and explore its potential as a target for therapy in GBM. The importance of the UPR in contributing to acute ER stress-induced cytotoxicity was examined, including effects on the self-renewal potential of GSCs and the underlying molecular mechanisms were elucidated. For this, previously in our lab generated and characterized patient-derived GSC-enriched GBM neurosphere models were employed. A novel noncanonical mechanism for PERK was identified that regulates differentiation and stemness in GSCs. We conclude that ER stress-inducing therapies and PERK modulation may provide promising therapeutic approaches in GBM.

U2 - 10.33612/diss.118411504

DO - 10.33612/diss.118411504

M3 - Thesis fully internal (DIV)

SN - 978-94-034-2469-9

PB - Rijksuniversiteit Groningen

CY - [Groningen]

ER -

The unfolded protein response in glioblastoma stem cells: towards new targets for therapy

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