Enhanced proteasomal activity is essential for long term survival and recurrence of innately radiation resistant residual glioblastoma cells.

Enhanced proteasomal activity is essential for long term survival and recurrence of innately radiation resistant residual glioblastoma cells.
Oncotarget. 2018 Jun 12;9(45):27667-27681
Authors: Rajendra J, Datta KK, Ud Din Farooqee SB, Thorat R, Kumar K, Gardi N, Kaur E, Nair J, Salunkhe S, Patkar K, Desai S, Goda JS, Moiyadi A, Dutt A, Venkatraman P, Gowda H, Dutt S
Abstract
Therapy resistance and recurrence in Glioblastoma is due to the presence of residual radiation resistant cells. However, because of their inaccessibility from patient biopsies, the molecular mechanisms driving their survival remain unexplored. Residual Radiation Resistant (RR) and Relapse (R) cells were captured using cellular radiation resistant model generated from patient derived primary cultures and cell lines. iTRAQ based quantitative proteomics was performed to identify pathways unique to RR cells followed by in vitro and in vivo experiments showing their role in radio-resistance. 2720 proteins were identified across Parent (P), RR and R population with 824 and 874 differential proteins in RR and R cells. Unsupervised clustering showed proteasome pathway as the most significantly deregulated pathway in RR cells. Concordantly, the RR cells displayed enhanced expression and activity of proteasome subunits, which triggered NFkB signalling. Pharmacological inhibition of proteasome activity led to impeded NFkB transcriptional activity, radio-sensitization of RR ...

Source: Oncotarget - July 4, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research