CCT2 enhances the proliferation and migration of head and neck squamous cell carcinoma via regulating cell cycle

Abstract

Recent therapeutic advances have improved the survival of head and neck squamous cell carcinoma (HNSCC) patients, but the prognosis of HNSCC remains dismal. Further understanding of the underlying mechanism of HNSCC progression is still an urgent need. In this study, bioinformatics-based analysis revealed that Chaperonin containing TCP-1, subunit 2 (CCT2) is significantly upregulated in HNSCC and related to pathoclinical outcomes, which is validated by the fact that four human HNSCC cell lines all express higher CCT2 than the normal oral squamous cell line. Clinically, high CCT2 expression was positively associated with worse overall survival (OS) and TNM classification in HNSCC patients. Further study indicated that suppression of CCT2 by RNA interference significantly inhibits cell proliferation, migration and invasion, arrests cell cycle at G2 phase, and prevents epithelial-mesenchymal transition (EMT) of both SAS and HSC-3 cell lines. In vivo assays further verified that CCT2 knockdown inhibited tumor growth in HNSCC. Moreover, knockdown of CCT2 led to the significant decrease of Cdc20 as well as cyclin D1, cyclin E1, and CDK6 while increase of GSK3-α/β and p27, which shed light into molecular mechanism of CCT2 function. In conclusion, elevated CCT2 expression promotes HNSCC cell proliferation via Cdc20 mediated cyclin-CDK pathway and CCT2 would be a valuable prognostic biomarker and therapeutic target in HNSCC.