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

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects Pub Date : 2024-06-01 DOI:10.1016/j.bbagen.2024.130650

Hiromu Seki , Kazuki Kitabatake , Sei-ichi Tanuma , Mitsutoshi Tsukimoto

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Abstract

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.

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RAGE 参与辐射诱导人类胶质母细胞瘤细胞获得恶性表型。

胶质母细胞瘤（GBM）是一种侵袭性极强的中枢神经系统恶性肿瘤，主要采用放射治疗。然而，由于辐照可能导致癌细胞获得迁移能力，从而促进肿瘤的转移和侵袭，因此了解细胞迁移增强的机制对于防止 GBM 复发非常重要。高级糖化终产物受体（RAGE）是一种由高迁移率基团框 1（HMGB1）激活的模式识别受体。在这项研究中，我们发现 RAGE 在γ-辐照对人 GBM A172 细胞的细胞迁移增强作用中发挥作用。γ-照射会诱导肌动蛋白重塑（一种获得运动能力的标记），并增强 A172 细胞的迁移。RAGE的特异性抑制剂（FPS-ZM1和TTP488）或敲除RAGE可抑制这两种表型。HMGB1抑制剂丙酮酸乙酯同样抑制了γ-辐照诱导的细胞迁移增强。此外，RAGE抑制剂抑制了γ-辐照诱导的STAT3磷酸化，STAT3抑制剂抑制了γ-辐照诱导的细胞迁移增强，表明STAT3参与了RAGE下游的迁移增强。我们的研究结果表明，HMGB1-RAGE-STAT3 信号转导参与了辐射诱导的 GBM 细胞迁移增强，并可能通过促进转移和侵袭导致 GBM 复发。

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来源期刊

Biochimica et biophysica acta. General subjects 生物-生化与分子生物学

CiteScore

6.40

自引率

0.00%

发文量

139

审稿时长

30 days

期刊介绍： BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.