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  2. 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

  • FASEB J. 2020 Jan;34(1):1481-1496. doi: 10.1096/fj.201901629RR.
Pei Liu 1 Chenchen Zhu 1 Juanjuan Luo 1 Sheng Lan 1 Dongsheng Su 1 Qiongjin Wang 1 Zhe Wei 2 Wei Cui 3 Chuan Xu 4 Xiaojun Yang 1
Affiliations

Affiliations

  • 1 Neuroscience Center, Shantou University Medical College, Shantou, China.
  • 2 Faculty of Medicine and Health, Lishui University, Lishui, China.
  • 3 Department of Pharmacology, College of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, Shenyang, China.
  • 4 Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Abstract

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.

Keywords

Par6; cell proliferation; cyclin D1; glioma.

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