Par6 regulates cell cycle progression through enhancement of Akt/PI3K/GSK-3β signaling pathway activation in glioma
Par6 regulates cell cycle progression through enhancement of Akt/PI3K/GSK-3β signaling pathway activation in glioma
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Par6 通过增强胶质瘤中 Akt/PI3K/GSK–3β 信号通路的激活来调节细胞周期进程
DOI：
10.1096/fj.201901629rr
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发表时间：
2020-01-01
期刊：
影响因子：
4.8
通讯作者：
Yang, Xiaojun
中科院分区：
文献类型：
--
作者：
Liu, Pei;Zhu, Chenchen;Yang, Xiaojun
Par6作为极性蛋白复合物的关键因子，不仅调控极化过程，而且在许多上皮恶性肿瘤的转移和进展中起重要作用。在这里，我们发现Par6是胶质瘤发生的一个重要组成部分。我们的结果表明Par6在恶性胶质瘤组织和细胞系中表达异常。我们发现，调节Par6的表达可诱导体内和体外的细胞增殖和肿瘤生长。此外，RNA‐seq显示Par6的作用与细胞周期蛋白D1调控的胶质瘤细胞周期进展有关。此外，我们的研究结果表明，Par6的调节可以增强Akt/PI3K信号通路的激活，从而上调GSK‐3β蛋白的表达水平，从而调节cyclin D1介导的细胞周期调节。此外，我们发现TGF‐β‐诱导的Par6表达上调可能参与了这一过程。病理分析证实了人胶质瘤组织中Par6的表达与预后的相关性，提示Par6的表达调控胶质瘤的发生和发展。因此，我们的研究结果表明，Par6可能是一种潜在的诊断生物标志物，并为恶性胶质瘤的治疗提供了一种治疗策略。
As the key factor of the polarity protein complex, Par6 not only regulates polarization processes, but also plays important roles in tumor metastasis and progression in many epithelium malignancy tumors. Here, we showed that Par6 is an essential component in glioma tumorigenesis. Our results indicated the aberrant expression of Par6 in malignant glioma tissues and cell lines. We found that the regulation of Par6 expression induces cell proliferation and tumor growth in vivo and in vitro. Additionally, RNA‐seq revealed the effects of Par6 were associated with cyclin D1‐regulated cell cycle progression in glioma cells. Moreover, our results demonstrated that the regulation of Par6 can enhance the activation of Akt/PI3K signaling pathway, and subsequently upregulate the expression level of GSK‐3β protein, which then regulate cyclin D1‐mediated cell cycle regulation. Furthermore, we found that TGF‐β‐induced the upregulation of Par6 expression may be involved in this process. The pathological analysis confirmed the correlation between Par6 expression and the prognosis in human glioma tissues, suggesting the regulation of Par6 expression regulates glioma tumorigenesis and progression. Thus, our findings showed that Par6 might be a potential biomarker for the diagnosis and providing a therapeutic strategy for the treatment of malignant glioma.