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

Problem: To determine the role of inactivated GSK3β with respect to Wnt/β-catenin pathway activation in HPV-16/18-associated cervical cancer.

Method Of Study: The expression of active (pGSK3β-Try(216)), inactive (pGSK3β-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 β-catenin and APC expression.

Results: The dramatic decrease of pGSK3β-Try(216) expression but ectopic overexpression of pGSK3β-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 β-catenin (P = 0.0001; P = 0.0001).

Conclusion: The process of generation of HPV-16-associated cervical tumorigenesis is synergized with GSK3β inactivation and overactivation of Wnt/β-catenin pathway.