Rajendra J, Ghorai A, Dutt S

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, ...

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and relapse cells using iTRAQ based quantitative proteomics of glioma cells. The proteomics data revealed significant up-regulation (fold change >1.5) of 14-3-3?, 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 14-3-3? radio-sensitized GBM cells and further stimulated therapy-induced senescence (TIS) and multinucleated giant cells (MNGCs) phenotype in RR cells. Intriguingly, 14-3-3? 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 14-3-3? from RR cells identified novel interacting partners of 14-3-3? involved in cellular metabolism. Taken together, here we identified novel interacting partners of 14-3-3? and proposed an unconventional function of 14-3-3? as a negative regulator of TIS and mitochondrial biogenesis in residual resistant cells and loss of which also radio-sensitize GBM cells.

Date: Nov. 01, 2021

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