title: Autocrine IL-8 promotes F-actin polymerization and mediate mesenchymal transition via ELMO1-NF-κB-Snail signaling in glioma.
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.
authors: a Department of Pathology ; Weifang Medical University ; Weifang , PR China.
authors: Baogang
authors: B
authors: Zhang
authors: Lihong
authors: L
authors: Shi
authors: Shijun
authors: S
authors: Lu
authors: Xiuning
authors: X
authors: Sun
authors: Yuqing
authors: Y
authors: Liu
authors: Hongli
authors: H
authors: Li
authors: Xuejian
authors: X
authors: Wang
authors: Chunzhen
authors: C
authors: Zhao
authors: Heng
authors: H
authors: Zhang
authors: Ying
authors: Y
authors: Wang
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019898:Autocrine Communication; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D060787:Neoplasm Grading; D011379:Prognosis; D011485:Protein Binding; D055503:Protein Multimerization; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism*; D055815:Young Adult; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C465214:ELMO1 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D023062:Receptors, Interleukin-8A; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020830:rac1 GTP-Binding Protein
keywords: ANT, adjacent nontumor tissues; CM, conditioned medium; CXCR1, chemokine (C-X-C motif) receptor 1; CXCR2, chemokine (C-X-C motif) receptor 2; Dock180, dedicator of cytokinesis; ELMO1, engulfment and cell motility 1; EMT, epithelial-mesenchymal transition;; ELMO1; IL-8; glioma; invasion