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16.04.2019 | Laboratory Investigation

Activation of STAT1 by the FRK tyrosine kinase is associated with human glioma growth

verfasst von: Lei Hua, Guanghui Wang, Zhen Wang, Jiale Fu, Zhen Fang, Ting Zhuang, Liang Zhao, Zhenkun Zong, Chengkun Ye, Hongmei Liu, Yufu Zhu, Rutong Yu

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2019

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Abstract

Purpose

Glioma is a highly aggressive and lethal brain tumor. Signal transducers and activators of transcription (STAT) pathway are widely implicated in glioma carcinogenesis. Our previous study found that the Fynrelated kinase (FRK) gene, plays as a tumor suppressor in the development and progression of glioma. This study aimed to investigate the role of FRK in the activation pathway of STATs and its effect on the growth of glioma.

Methods

The U251 and U87 cells with stable FRK overexpression were generated by lentivirus technique. The effects of FRK on the related proteins of STAT signaling pathway were detected by western blotting. Coimmunoprecipitation was used to detect the association of FRK and STAT1. The effects of STAT1 on the proliferation of glioma cells were detected by CCK8 or Edu cell proliferation assays. The expressions and correlation of FRK and p-STAT1 in glioma tissues were detectd by western blotting or immunohistochemistry. The effect of FRK on the growth of glioma was investigated in vivo mouse model.

Results

The level of p-JAK2 and p-STAT1 increased after FRK overexpression, while they decreased after FRK downregulation both in U251 and U87 cells. However, FRK had no effect on STAT3 phosphorylation. FRK-induced STAT1 activation was not dependent on JAK2. FRK associated with STAT1, induced STAT1 nuclear translocation and regulated the expressions of STAT1-related target genes. STAT1 overexpression suppressed the proliferation of glioma cells. In contrast, STAT1 knockdown by siRNA promoted glioma cell growth. Importantly, down-regulation of STAT1 partially attenuated FRK-induced growth suppression. The clinical sample-based study indicated that the expression of FRK was significantly correlated with the expression of p-STAT1. FRK significantly inhibited glioma tumor growth in vivo.

Conclusions

Our findings highlighted a critical role of FRK in tumor suppression ability through promoting STAT1 activation, and provided a potential therapeutic target for glioma.

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Titel: Activation of STAT1 by the FRK tyrosine kinase is associated with human glioma growth
verfasst von: Lei Hua
Guanghui Wang
Zhen Wang
Jiale Fu
Zhen Fang
Ting Zhuang
Liang Zhao
Zhenkun Zong
Chengkun Ye
Hongmei Liu
Yufu Zhu
Rutong Yu
Publikationsdatum: 16.04.2019
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2019
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03143-w

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Activation of STAT1 by the FRK tyrosine kinase is associated with human glioma growth

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Purpose

Methods

Results

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