title: Downregulation of TRAP1 sensitizes glioblastoma cells to temozolomide chemotherapy through regulating metabolic reprogramming.
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.
authors.affiliation: aDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University bBrain Science Institute of Harbin Medical University cDepartment of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, People's Republic of China dDepartment of Acupuncture, Takarazuka University of Medical and Health Care, Takarazuka City, Japan.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wu
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Liu
authors.forename: KenKa
authors.initials: K
authors.lastname: Cho
authors.forename: Xingli
authors.initials: X
authors.lastname: Dong
authors.forename: Lei
authors.initials: L
authors.lastname: Teng
authors.forename: Dayong
authors.initials: D
authors.lastname: Han
authors.forename: Huailei
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Hou
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.forename: Yunke
authors.initials: Y
authors.lastname: Bi
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018841:HSP90 Heat-Shock Proteins; C092306:TRAP1 protein, human; D003606:Dacarbazine; D000077204:Temozolomide