Autocrine IL-8 promotes F-actin polymerization and mediate mesenchymal transition via ELMO1-NF-κB-Snail signaling in glioma

自分泌 IL-8 促进 F-肌动蛋白聚合并通过 ELMO1-NF-κB-Snail 信号传导介导胶质瘤中的间充质转化

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作者:Baogang Zhang, Lihong Shi, Shijun Lu, Xiuning Sun, Yuqing Liu, Hongli Li, Xuejian Wang, Chunzhen Zhao, Heng Zhang, Ying Wang

Abstract

Glioma is the most common form of primary malignant brain cancers. Tumor cell invasiveness is a critical challenge in the clinical management of glioma patients. The invasive biological feature of glioma cell is stimulated by both autocrine and paracrine factors including chemokine IL-8. In this study, we report that the production of IL-8 is higher in glioma tissues and cells than adjacent nontumor tissues (ANT) and normal glial cells. Autocrine IL-8 can increase the invasive ability of glioma cells by binding to CXCR1. In addition, high expression of IL-8 indicates poor prognosis of glioma patients. Furthermore, IL-8 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeletal reorganisation in an ELMO1 dependent manner. Finally, we found that IL-8 could enhance mesenchymal transition(MT) of glioma cells by activating ELMO1-NF-κB-Snail signaling. Our data indicate that IL-8 autocrine is responsible for the invasive phenotype of glioma and IL-8 may be a useful prognostic marker for glioma and novel therapeutic target for glioma invasion intervention.

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