Involvement of RAGE in radiation-induced acquisition of malignant phenotypes in human glioblastoma cells

Glioblastoma (GBM), a highly aggressive malignant tumor of the central nervous system, is mainly treated with radiotherapy. However, since irradiation may lead to the acquisition of migration ability by cancer cells, thereby promoting tumor metastasis and invasion, it is important to understand the...

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Bibliographic Details
Published in:Biochimica et biophysica acta. General subjects Vol. 1868; no. 9; p. 130650
Main Authors: Seki, Hiromu, Kitabatake, Kazuki, Tanuma, Sei-ichi, Tsukimoto, Mitsutoshi
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.09.2024
Subjects:
actin
Benzamides
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Brain Neoplasms - radiotherapy
Cell Line, Tumor
Cell migration
cell movement
Cell Movement - radiation effects
central nervous system
Gamma Rays
Glioblastoma
Glioblastoma - metabolism
Glioblastoma - pathology
Glioblastoma - radiotherapy
HMGB1
HMGB1 Protein - metabolism
Humans
irradiation
metastasis
nucleoproteins
Phenotype
phosphorylation
Phosphorylation - radiation effects
Pyruvates - pharmacology
pyruvic acid
Radiation
radiotherapy
RAGE
Receptor for Advanced Glycation End Products - metabolism
Signal Transduction
STAT3
STAT3 Transcription Factor - metabolism
RAGE
HMGB1
Cell migration
Glioblastoma
Radiation
STAT3
ISSN:0304-4165, 1872-8006, 1872-8006
Online Access:Get full text
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Summary:Glioblastoma (GBM), a highly aggressive malignant tumor of the central nervous system, is mainly treated with radiotherapy. However, since irradiation may lead to the acquisition of migration ability by cancer cells, thereby promoting tumor metastasis and invasion, it is important to understand the mechanism of cell migration enhancement in order to prevent recurrence of GBM. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor activated by high mobility group box 1 (HMGB1). In this study, we found that RAGE plays a role in the enhancement of cell migration by γ-irradiation in human GBM A172 cells. γ-Irradiation induced actin remodeling, a marker of motility acquisition, and enhancement of cell migration in A172 cells. Both phenotypes were suppressed by specific inhibitors of RAGE (FPS-ZM1 and TTP488) or by knockdown of RAGE. The HMGB1 inhibitor ethyl pyruvate similarly suppressed γ-irradiation-induced enhancement of cell migration. In addition, γ-irradiation-induced phosphorylation of STAT3 was suppressed by RAGE inhibitors, and a STAT3 inhibitor suppressed γ-irradiation-induced enhancement of cell migration, indicating that STAT3 is involved in the migration enhancement downstream of RAGE. Our results suggest that HMGB1-RAGE-STAT3 signaling is involved in radiation-induced enhancement of GBM cell migration, and may contribute to GBM recurrence by promoting metastasis and invasion. [Display omitted] •γ-Radiation induces enhanced migration of human glioblastoma cells.•RAGE and RAGE ligands are involved in radiation-induced cell migration.•STAT3 signaling is involved in radiation-induced cell migration.•Radiation-induced phosphorylation of STAT3 is mediated by RAGE.•HMGB1-RAGE-STAT3 signaling is involved in radiation-enhanced cell migration.
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ISSN:0304-4165
1872-8006
1872-8006
DOI:10.1016/j.bbagen.2024.130650