Par6 regulates cell cycle progression through enhancement of Akt/PI3K/GSK‐3β signaling pathway activation in glioma

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.

RETRACTED ARTICLE: MYC-mediated upregulation of PNO1 promotes glioma tumorigenesis by activating THBS1/FAK/Akt signaling

“…5A). Many intersection DEGs, including CCND1, RAC1, PRKCA, THBS1, and AKT3, have been reported to involve in glioma tumorigenesis [18][19][20][21][22][23] and were further confirmed by RT-PCR in U251-shPNO1 cells (Fig. 5B).…”

Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells

“…In addition, the regulatory role of Akt in cell proliferation has also been reported to occur through various downstream effectors. For example, Akt activation induces GSK3b/cyclinD1-mediated cell proliferation [ 49 ]. Akt signaling was shown to downregulate p27, a cyclin-dependent kinase inhibitor that induces cell cycle arrest [ 50 ]; in contrast, attenuation of Akt function conversely increases p27-suppressed cancer cell growth [ 51 ].…”

Alpinetin inhibits macrophage infiltration and atherosclerosis by improving the thiol redox state: Requirement of GSk3β/Fyn‐dependent Nrf2 activation

“…Nrf2 nuclear accumulation is also affected by its nuclear export, which is regulated through phosphorylation at tyrosine 568 in the nucleus by a pathway involving glycogen synthase kinase 3 beta (GSK‐3β) and the Src family member, Fyn kinase. GSK‐3β is a ubiquitously expressed and constitutively active Ser/Thr protein kinase that regulates cell metabolism and is known to be involved in human disorders, such as diabetes, cancer, neurodegeneration, and atherosclerosis 11–14 . GSK‐3β, a Keap1‐independent Nrf2 regulator, directly phosphorylates Nrf2, leading to nuclear exclusion 15 .…”

“…GSK-3β is a ubiquitously expressed and constitutively active Ser/Thr protein kinase that regulates cell metabolism and is known to be involved in human disorders, such as diabetes, cancer, neurodegeneration, and atherosclerosis. [11][12][13][14] GSK-3β, a Keap1independent Nrf2 regulator, directly phosphorylates Nrf2, leading to nuclear exclusion. 15 In addition, GSK-3β can also act upstream of Fyn kinase, which increases Fyn phosphorylation and nuclear retention.…”