Differential Wnt-β- catenin pathway activation in HPV positive and negative oral epithelium is transmitted during head and neck tumorigenesis: clinical implications

• Published in: Medical microbiology and immunology Vol. 210; no. 1; pp. 49 - 63
• Main Authors: Chakraborty, Balarko, Mukhopadhyay, Debalina, Roychowdhury, Anirban, Basu, Mukta, Alam, Neyaz, Chatterjee, Kabita, Chakrabarti, Jayanta, Panda, Chinmay Kumar
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2021; Springer Nature B.V
• Subjects: Antagonists; Biomedical and Life Sciences; Biomedicine; Dkk1 protein; DNMT1 protein; Epithelium; Frizzled-related protein 1; Head & neck cancer; Human papillomavirus; Immunology; Medical Microbiology; Original Investigation; Squamous cell carcinoma; Tobacco; Tumorigenesis; Tumors; Virology; Wnt protein; β-Catenin; E7; SFRP1; Oral epithelium; SFRP2; FZD7; Head and neck cancer; Basal–parabasal layers; DKK1; HPV; LRP6
• ISSN: 0300-8584; 1432-1831; 1432-1831
• DOI: 10.1007/s00430-020-00697-9

The aim of this study is to understand the association of HPV infection and wnt-β-catenin self-renewal pathway in development of head and neck squamous cell carcinoma (HNSCC). For this reason, the molecular profiles (methylation/deletion/expression) of antagonists (SFRP1/2 and DKK1), agonists (FZD7 and LRP6) and effector protein β-catenin of the pathway were analyzed in HPV positive/negative oral epithelium at first, followed by its changes during development of the tumor along with correlations with different clinico-pathological parameters. HPV infection alone or in combination with tobacco habit could activate p- β-catenin expression in basal/parabasal layers of oral epithelium through high expression of FZD7 and significant down regulation of SFRP1/2 through promoter hypermethylation due to over expression of DNMT1 with ubiquitous down regulation of DKK1 and up-regulation of LRP6. This phenomenon has been seen in respective HPV positive and negative HNSCC tumors with additional deletion/microsatellite size alterations in the antagonists. Overall alterations (methylation/deletion) of SFRP1/2, DKK1 gradually increased from Group I (HPV-/Tobacco-) to Group IV(HPV+/Tobacco+) tumors, leading to the worst prognosis of the patients. Thus, the transmission of differentially activated wnt-β-catenin pathway from HPV positive/negative basal/parabasal layers of oral epithelium to HNSCC tumors determines differences in molecular pathogenesis of the disease.