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01.09.2009 | Laboratory Investigation - HUman/Animal Tissue

Upregulation of LRIG1 suppresses malignant glioma cell growth by attenuating EGFR activity

verfasst von: Fei Ye, Qinglei Gao, Tongjiang Xu, Liang Zeng, Yibo Ou, Feng Mao, Heping Wang, Yue He, Baofeng Wang, Zhengming Yang, Dongsheng Guo, Ting Lei

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2009

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Abstract

Activated epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target for a variety of solid tumors, particularly malignant gliomas. A recently discovered transmembrane glycoprotein, LRIG1, antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases and acts as a negative feedback loop of EGFR and proposed tumor suppressors. The aim of this study was to investigate the impact of LRIG1 on the biological features of glioma cells and the possible mechanisms of enhanced apoptosis induced by upregulation of LRIG1. We observed that the expression of LRIG1 was decreased, while the expression of EGFR was increased in the majority of astrocytomas, and the ratio of EGFR/LRIG1 was increased by sixfold in tumors versus corresponding non-neoplastic tissue. Upregulation of LRIG1, followed by a decrease of EGFR on the cytomembrane of the cells, induced cell apoptosis and cell growth inhibition, and further reversed invasion in glioma cell lines and primary glioma cells. Our study now clearly indicates that LRIG1 indeed affects cell fate and biology behaviors of the cells in vitro by inhibiting phosphorylation of downstream MAPK and AKT signaling pathway, and the elevated release level of caspase-8 might contribute to the enhanced apoptosis in LRIG1 transfected glioma cells. Taken together, these findings provide us with an insight into LRIG1 function, and we conclude that LRIG1 evolved in gliomas as a rare feedback negative attenuator of EGFR and could offer a novel therapeutic target to treat patients with malignant gliomas.

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Titel: Upregulation of LRIG1 suppresses malignant glioma cell growth by attenuating EGFR activity
verfasst von: Fei Ye
Qinglei Gao
Tongjiang Xu
Liang Zeng
Yibo Ou
Feng Mao
Heping Wang
Yue He
Baofeng Wang
Zhengming Yang
Dongsheng Guo
Ting Lei
Publikationsdatum: 01.09.2009
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 2/2009
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-009-9836-1

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