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Par6 regulates cell cycle progression through enhancement of Akt/PI3K/GSK‐3β signaling pathway activation in glioma
Author(s) -
Liu Pei,
Zhu Chenchen,
Luo Juanjuan,
Lan Sheng,
Su Dongsheng,
Wang Qiongjin,
Wei Zhe,
Cui Wei,
Xu Chuan,
Yang Xiaojun
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901629rr
Subject(s) - glioma , cell cycle , carcinogenesis , pi3k/akt/mtor pathway , cancer research , downregulation and upregulation , biology , cyclin d1 , protein kinase b , tumor progression , signal transduction , cell , microbiology and biotechnology , cancer , gene , biochemistry , genetics
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.