title: LRIG1 enhances the radiosensitivity of radioresistant human glioblastoma U251 cells via attenuation of the EGFR/Akt signaling pathway.
abstract: The radiotherapy as a local and regional modality is widely applied in treatment of glioma, but most glioblastomas are commonly resistant to irradiation treatment. It remains challengeable to seek out efficient strategies to conquer the resistance of human glioblastoma cells to radiotherapy. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a newly discovered tumor suppressor which involved in regulation of chemosensitivity in various human cancer cells. In the present study, we established a radioresistant U251 cell line (U251R) to investigate the role of LRIG1 in regulation of radiosensitivity in human glioblastoma cells. Significantly decreased expression level of LRIG1 and enhanced expression of EGFR and phosphorylated Akt were detected in U251R cells compared with the parental U251 cells. U251R cells exhibited an advantage in colony formation ability, which accompanied by remarkably reduced X-ray-induced γ-H2AX foci formation and cell apoptosis. LRIG1 overexpression significantly inhibited the colony formation ability of U251R cells and obviously enhanced X-ray-inducedγ-H2AX foci formation and cell apoptosis. In addition, up-regulated expression of LRIG1 suppressed the expression level of EGFR and phosphorylated Akt protein. Our results demonstrated that LRIG1 expression was related to the radiosensitivity of human glioblastoma cells and may play an important role in the regulation of cellular radiosensitivity of human glioblastoma cells through the EGFR/Akt signaling pathway.
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Ji-An
authors.initials: JA
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Bao-Hui
authors.initials: BH
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Ling-Min
authors.initials: LM
authors.lastname: Shao
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Zhen-Tao
authors.initials: ZT
authors.lastname: Guo
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Li-Quan
authors.initials: LQ
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Shen-Qi
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
authors.forename: Qian-Xue
authors.initials: QX
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D015398:Signal Transduction
chemical_list: C484445:LRIG1 protein, human; D008562:Membrane Glycoproteins; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR signaling; LRIG1; apoptosis; glioblastoma; radiosensitivity; γ-H2AX