14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells

Glioblastoma (GBM) is the most lethal primary brain tumour with a median survival of only 15 months. We have previously demonstrated the generation of an in vitro therapy resistance model that captures the residual resistant (RR) disease cells of GBM post-radiation. We also reported the proteomic la...

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Autores principales:	Jacinth Rajendra, Atanu Ghorai, Shilpee Dutt
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	14-3-3ζ Glioblastoma Therapy induced senescence Mitochondrial biogenesis MNGCs Science (General) Q1-390 Social sciences (General) H1-99
Acceso en línea:	https://doaj.org/article/bd22e5e60c2b4845ac22d4f11f2318c0
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spelling	oai:doaj.org-article:bd22e5e60c2b4845ac22d4f11f2318c02021-12-02T05:02:53Z14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells2405-844010.1016/j.heliyon.2021.e08371https://doaj.org/article/bd22e5e60c2b4845ac22d4f11f2318c02021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405844021024749https://doaj.org/toc/2405-8440Glioblastoma (GBM) is the most lethal primary brain tumour with a median survival of only 15 months. We have previously demonstrated the generation of an in vitro therapy resistance model that captures the residual resistant (RR) disease cells of GBM post-radiation. We also reported the proteomic landscape of parent, residual, and relapse cells using iTRAQ based quantitative proteomics of glioma cells. The proteomics data revealed significant up-regulation (fold change >1.5) of 14-3-3ζ, specifically in GBM RR cells. This was further confirmed by western blots in residual cells generated from GBM cell lines and patient sample-derived short-term primary culture. ShRNA-mediated knockdown of 14-3-3ζ radio-sensitized GBM cells and further stimulated therapy-induced senescence (TIS) and multinucleated giant cells (MNGCs) phenotype in RR cells. Intriguingly, 14-3-3ζ knockdown residual cells also showed a significantly higher number of mitochondria and increased mtDNA content. Indeed, in vitro GST pull-down mass spectrometry analysis of GST tagged 14-3-3ζ from RR cells identified novel interacting partners of 14-3-3ζ involved in cellular metabolism. Taken together, here we identified novel interacting partners of 14-3-3ζ and proposed an unconventional function of 14-3-3ζ as a negative regulator of TIS and mitochondrial biogenesis in residual resistant cells and loss of which also radio-sensitize GBM cells.Jacinth RajendraAtanu GhoraiShilpee DuttElsevierarticle14-3-3ζGlioblastomaTherapy induced senescenceMitochondrial biogenesisMNGCsScience (General)Q1-390Social sciences (General)H1-99ENHeliyon, Vol 7, Iss 11, Pp e08371- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	14-3-3ζ Glioblastoma Therapy induced senescence Mitochondrial biogenesis MNGCs Science (General) Q1-390 Social sciences (General) H1-99
spellingShingle	14-3-3ζ Glioblastoma Therapy induced senescence Mitochondrial biogenesis MNGCs Science (General) Q1-390 Social sciences (General) H1-99 Jacinth Rajendra Atanu Ghorai Shilpee Dutt 14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells
description	Glioblastoma (GBM) is the most lethal primary brain tumour with a median survival of only 15 months. We have previously demonstrated the generation of an in vitro therapy resistance model that captures the residual resistant (RR) disease cells of GBM post-radiation. We also reported the proteomic landscape of parent, residual, and relapse cells using iTRAQ based quantitative proteomics of glioma cells. The proteomics data revealed significant up-regulation (fold change >1.5) of 14-3-3ζ, specifically in GBM RR cells. This was further confirmed by western blots in residual cells generated from GBM cell lines and patient sample-derived short-term primary culture. ShRNA-mediated knockdown of 14-3-3ζ radio-sensitized GBM cells and further stimulated therapy-induced senescence (TIS) and multinucleated giant cells (MNGCs) phenotype in RR cells. Intriguingly, 14-3-3ζ knockdown residual cells also showed a significantly higher number of mitochondria and increased mtDNA content. Indeed, in vitro GST pull-down mass spectrometry analysis of GST tagged 14-3-3ζ from RR cells identified novel interacting partners of 14-3-3ζ involved in cellular metabolism. Taken together, here we identified novel interacting partners of 14-3-3ζ and proposed an unconventional function of 14-3-3ζ as a negative regulator of TIS and mitochondrial biogenesis in residual resistant cells and loss of which also radio-sensitize GBM cells.
format	article
author	Jacinth Rajendra Atanu Ghorai Shilpee Dutt
author_facet	Jacinth Rajendra Atanu Ghorai Shilpee Dutt
author_sort	Jacinth Rajendra
title	14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells
title_short	14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells
title_full	14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells
title_fullStr	14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells
title_full_unstemmed	14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells
title_sort	14-3-3ζ negatively regulates mitochondrial biogenesis in gbm residual cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/bd22e5e60c2b4845ac22d4f11f2318c0
work_keys_str_mv	AT jacinthrajendra 1433znegativelyregulatesmitochondrialbiogenesisingbmresidualcells AT atanughorai 1433znegativelyregulatesmitochondrialbiogenesisingbmresidualcells AT shilpeedutt 1433znegativelyregulatesmitochondrialbiogenesisingbmresidualcells
_version_	1718400733996384256

14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells

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