LRIG3 modulates proliferation, apoptosis and invasion of glioblastoma cells as a potent tumor suppressor

Abstract Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3 gene is mapped to chromosome 12q13.2, a region that is frequently deleted in a subset of glioblastoma multiforme (GBM). It has been reported that perinuclear LRIG3 staining correlated with low WHO grade of glioma and better survi...

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Bibliographic Details
Published in:Journal of the neurological sciences 2015-03, Vol.350 (1), p.61-68
Main Authors: Guo, Dongsheng, Yang, Hongkuan, Guo, Yang, Xiao, Qungen, Mao, Feng, Tan, Yihu, Wan, Xueyan, Wang, Baofeng, Lei, Ting
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - physiology
Cell Line, Tumor
Cell Proliferation - physiology
EGFR
Female
Genes, Tumor Suppressor - physiology
Glioblastoma
Glioblastoma - metabolism
Glioblastoma - pathology
Glioblastoma - prevention & control
Humans
Invasion
LRIG3
Membrane Proteins - biosynthesis
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness - pathology
Neoplasm Invasiveness - prevention & control
Neurology
Proliferation
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - biosynthesis
Xenograft Model Antitumor Assays - methods
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Summary:Abstract Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3 gene is mapped to chromosome 12q13.2, a region that is frequently deleted in a subset of glioblastoma multiforme (GBM). It has been reported that perinuclear LRIG3 staining correlated with low WHO grade of glioma and better survival of the patients. However, the relationship between LRIG3 and glioma is not very clear. The purpose of this study is to demonstrate the impacts of LRIG3 on biological characteristics of glioma and its possible mechanisms. We found that transduction of LRIG3 into glioblastoma cells inhibited cell growth in vitro and in vivo , promoted cell apoptosis, and restrained cell invasion and migration. Further studies demonstrated that LRIG3 negatively regulated the epidermal growth factor receptor (EGFR) signaling pathway. Inhibition of EGFR could reduce the effects of LRIG3 knockdown on cell proliferation and EGFR signaling pathway. In conclusion, LRIG3 functions as a tumor suppressor by attenuating EGFR signaling pathway and the restoration of LRIG3 may offer therapeutic potential against malignant gliomas.
ISSN:0022-510X
1878-5883
DOI:10.1016/j.jns.2015.02.015