RRC ID 52241
Author Kikuchi R, Sampetrean O, Saya H, Yoshida K, Toda M.
Title Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells.
Journal J Neurooncol
Abstract DEP domain containing 1 (DEPDC1) is a novel oncoantigen expressed in cancer cells, which presents oncogenic activity and high immunogenicity. Although DEPDC1 has been predicted to be a useful antigen for the development of a cancer vaccine, its pathophysiological roles in glioma have not been investigated. Here, we analyzed the expression and function of DEPDC1 in malignant glioma. DEPDC1 expression in glioma cell lines, glioma tissues, and brain tumor initiating cells (BTICs) was assessed by western blot and quantitative polymerase chain reaction (PCR). The effect of DEPDC1 downregulation on cell growth and nuclear factor kappa B (NFκB) signaling in glioma cells was investigated. Overall survival was assessed in mouse glioma models using human glioma cells and induced mouse brain tumor stem cells (imBTSCs) to determine the effect of DEPDC1 suppression in vivo. DEPDC1 expression was increased in glioma cell lines, tissues, and BTICs. Suppression of endogenous DEPDC1 expression by small interfering RNA (siRNA) inhibited glioma cell viability and induced apoptosis through NFκB signaling. In mouse glioma models using human glioma cells and imBTSCs, downregulation of DEPDC1 expression prolonged overall survival. These results suggest that DEPDC1 represents a target molecule for the treatment of glioma.
Volume 133(2)
Pages 297-307
Published 2017-6
DOI 10.1007/s11060-017-2457-1
PII 10.1007/s11060-017-2457-1
PMID 28555424
MeSH Animals Brain Neoplasms / genetics Brain Neoplasms / metabolism* Brain Neoplasms / pathology Cell Line, Tumor Cell Proliferation / drug effects Cell Proliferation / genetics Cell Survival / physiology Female GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Gene Expression Regulation, Neoplastic / genetics* Glioma / metabolism* Glioma / pathology Humans Male Mice Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Neoplastic Stem Cells / metabolism* Neoplastic Stem Cells / pathology RNA, Messenger / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Repressor Proteins / metabolism Time Factors
IF 3.06
Times Cited 6
Resource
Human and Animal Cells U251(RCB0461)