PCDH8 inhibits glioma cell proliferation by negatively regulating the AKT/GSK beta/beta-catenin signaling pathway

摘要

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-alpha serine/threonine-protein kinase (AKT) [Threonine (T)308/Serine (S)473] and p-glycogen synthase kinase-3 beta(p-GSK3(3) (S9) protein expression, thereby reducing the level of (beta-catenin when compared with the control. By contrast, silencing of PCDH8 increased levels of p-AKT (T308/S473) and p-GSK3 beta (S9), thereby increasing the level of beta-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/beta-catenin signaling pathway and therefore promote glioma cell proliferation.