PCDH8 inhibits glioma cell proliferation by negatively regulating the AKT/GSK3β/β-catenin signaling pathway

Abstract

Protocadherin-8 (PCDH8), a member of the protocadherin superfamily of proteins, is frequently lost in numerous types of cancer. However, the role that PCDH8 serves in human glioma, and the molecular mechanisms underlying this, remain unclear. Data from the present study demonstrated that the expression levels of PCDH8 mRNA and protein were significantly decreased in human glioma tissue compared with normal brain tissue. This suggested that PCDH8 is associated with the development of glioma. Thus, the role of PCDH8 in glioma cell proliferation was investigated by silencing and overexpressing PCDH8 in U251 glioma cells. Overexpression of PCDH8 significantly inhibited glioma cell proliferation, while silencing of PCDH8 using small interfering RNA promoted glioma cell proliferation. Restoration of PCDH8 decreased phosphorylated (p)-Rac-α serine/threonine-protein kinase (AKT) [Threonine (T)308/Serine (S)473] and p-glycogen synthase kinase-3β (p-GSK3β) (S9) protein expression, thereby reducing the level of β-catenin when compared with the control. By contrast, silencing of PCDH8 increased levels of p-AKT (T308/S473) and p-GSK3β (S9), thereby increasing the level of β-catenin. In conclusion, the results of the present study suggested that PCDH8 suppressed glioma cell proliferation, and that the loss of PCDH8 may stimulate the proto-oncogene Wnt/β-catenin signaling pathway and therefore promote glioma cell proliferation.

Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt/GSK3β/β-Catenin Signaling Pathways

“…Currently, there are numerous reports about the close relationship between PI3K/Akt (phosphatidylinositide 3-kinases/protein kinase B) signal pathway and GSK3β [ 42 , 43 , 44 , 45 , 46 ]. Activated Akt can phosphorylate GSK3β resulting in inactivating GSK3β and inhibit the degradation of β-catenin [ 47 ].…”

Retracted Article: Overexpression of PCDH8 inhibits proliferation and invasion, and induces apoptosis in papillary thyroid cancer cells

“…[10][11][12] Most recently, one study showed that the expression levels of PCDH8 were signicantly decreased in human glioma tissues, and restoration of PCDH8 markedly inhibited glioma cell proliferation in vitro. 13 However, the biological roles of PCDH8 in PTC and the related mechanisms remain unclear. Therefore, in the present study, we detected the expression of PCDH8 in human PTC tissues and cell lines, and evaluated its role in PTC progression.…”

Proximity-dependent proteomics reveals extensive interactions of Protocadherin-19 with regulators of Rho GTPases and the microtubule cytoskeleton

“…However, several observations also suggest that the δ-pcdhs regulate the proliferation of neural progenitor cells and the production of neurons (Cooper et al, 2015;Zhang et al, 2014). These results are bolstered by observations implicating the δ-pcdhs as tumor suppressors in a variety of cancers (Xu et al, 2015;Yin et al, 2016;Zong et al, 2017), where forced expression of the δ-pcdhs can inhibit cell proliferation in cancer cell lines. The mechanisms by which δ-pcdhs could regulate proliferation are not known.…”

“…In several cases, the loss of δ-pcdh expression correlates with poor prognosis (Bing et al, 2018;Cao et al, 2018;Dang et al, 2016;Lin et al, 2018). In addition, evidence for a tumor suppressive role of the δ-pcdhs has been obtained in vitro, as their forced expression limits tumor growth (Xu et al, 2015;Yin et al, 2016;Zong et al, 2017).…”