CCT2 enhances c-Myc stabilization to drive tumor progression and chemoresistance in head and neck squamous cell carcinoma

CCT2, a vital subunit of the chaperonin-containing TCP-1 (CCT) complex, has emerged as a critical regulator of protein homeostasis and cancer progression. In this study, we highlight the essential role of CCT2 in head and neck squamous cell carcinoma (HNSCC), where it is overexpressed and strongly associated with poor prognosis, advanced clinical stages, and aggressive tumor behavior. Mechanistically, CCT2 interacts with and stabilizes the oncogenic c-Myc protein to drive tumor cell proliferation, migration, and invasion. Furthermore, CCT2 contributes to cisplatin resistance by regulating c-Myc-dependent pathways and cell cycle-related proteins. Notably, apoptotic vesicles derived from drug-resistant tumor cells transfer CCT2 to neighboring cells, further enhancing chemoresistance. These findings position CCT2 as a key driver of HNSCC progression and c-Myc-mediated oncogenic pathways, presenting it as a promising therapeutic target for overcoming drug resistance and improving treatment outcomes in HNSCC patients.