Clinical Significance of Inactivated Glycogen Synthase Kinase 3β in HPV-Associated Cervical Cancer: Relationship with Wnt/β-Catenin Pathway Activation

ProblemTo determine the role of inactivated GSK3 with respect to Wnt/-catenin pathway activation in HPV-16/18-associated cervical cancer. Method of studyThe expression of active (pGSK3-Try(216)), inactive (pGSK3-Ser(9)), and c-Myc as well as HPV-16/18 infection was analyzed in cervical intra-epithelial neoplasia (CIN), squamous cell carcinoma (SCCs) and normal by immunohistochemistry and multiplex PCR. The proteins level was also compared with -catenin and APC expression. ResultsThe dramatic decrease of pGSK3-Try(216) expression but ectopic overexpression of pGSK3-Ser(9) and c-Myc was observed both in CIN and SCCs samples compared to normal tissues. 57/67 CIN and 132/153 SCCs showed HPV-16 infection, while 3/67 CIN and 4/153 SCCs were harbored with HPV-18 infection. Both the proteins were significantly upregulated in HPV-16 infected cases (P=0.0001; P=0.001) and also positively correlated with nuclear -catenin (P=0.0001; P=0.0001). ConclusionThe process of generation of HPV-16-associated cervical tumorigenesis is synergized with GSK3 inactivation and overactivation of Wnt/-catenin pathway.