RRC ID 62779
Author Wu J, Liu Y, Cho K, Dong X, Teng L, Han D, Liu H, Chen X, Chen X, Hou X, Peng F, Bi Y, Shen C, Zhao S.
Title Downregulation of TRAP1 sensitizes glioblastoma cells to temozolomide chemotherapy through regulating metabolic reprogramming.
Journal Neuroreport
Abstract Cancer cells preferentially use aerobic glycolysis to support growth, a metabolic alteration commonly referred to as the 'Warburg effect.' Here, we show that the tumor necrosis factor receptor-associated protein 1 (TRAP1) is crucial for the Warburg effect in human glioblastoma multiforme (GBM). In contrast to normal brain, GBMs show increased TRAP1 expression. We used both GBM cell lines and neurospheres derived from human GBM specimens to examine the effects of Knockdown of TRAP1 on GBM cell lines and glioma stem cells. We also used a neurosphere recovery assay that measured neurosphere formation at three time points to assess the capacity of the culture to repopulate after knockdown of TRAP1. Our results showed that knockdown of TRAP1 strongly decreased GBM cell proliferation and migration, inhibited neurosphere recovery, secondary neurosphere formation, and enhanced the therapeutic effect of temozolomide in neurosphere cultures. In GBM, knockdown of TRAP1 appeared to inhibit tumor growth and migration through its regulatory effects on metabolic reprogramming.
Volume 27(3)
Pages 136-44
Published 2016-2-10
DOI 10.1097/WNR.0000000000000513
PMID 26716385
MeSH Antineoplastic Agents, Alkylating / pharmacology* Cell Line, Tumor / drug effects Cell Line, Tumor / metabolism Dacarbazine / analogs & derivatives* Dacarbazine / pharmacology Down-Regulation Glioblastoma / drug therapy Glioblastoma / metabolism* HSP90 Heat-Shock Proteins / metabolism HSP90 Heat-Shock Proteins / physiology* Humans Neoplastic Stem Cells / drug effects Neoplastic Stem Cells / metabolism Neural Stem Cells / drug effects Neural Stem Cells / metabolism Temozolomide
IF 1.394
Human and Animal Cells U-87 MG(RCB0419) U251(RCB0461)