CCT3 promotes cervical cancer lymph node metastasis through upregulation and functional activation of the PI3K/AKT pathway

Cervical cancer remains a leading cause of cancer-related mortality in women worldwide, with lymph node metastasis (LNM) being a primary determinant of poor prognosis. There is an urgent need to identify novel drivers of metastasis and actionable therapeutic targets. The GEPIA database was used to identify key genes and signaling pathways associated with tumor metastasis in cervical cancer. The functional role of Chaperonin Containing TCP1 Subunit 3 (CCT3) in promoting LNM was examined through in vitro and in vivo experiments. Clinical data from patients with cervical cancer were retrospectively reviewed to evaluate the prognostic value of CCT3 expression for predicting metastasis and survival. Bioinformatic analysis revealed that CCT3 was upregulated in cervical cancer tissues compared to normal cervix, and its high expression was associated with recurrence and overall survival. Pathway enrichment analysis indicated a significant role for the PI3K/AKT signaling pathway in cervical cancer progression. Functional assays demonstrated that CCT3 enhanced the motility, migration, and invasion of cervical cancer cells by upregulating and activating the PI3K/AKT pathway in vitro. Consistently, CCT3 overexpression promoted LNM in a mouse xenograft model in vivo. Immunohistochemical analysis of xenograft tissues confirmed that CCT3 overexpression activated the PI3K/AKT pathway in both primary tumors and metastatic lymph nodes. A key finding was that CCT3 not only increased the phosphorylation of PI3K and AKT but also upregulated their total mRNA and protein levels. In the clinical cohort, cytoplasmic CCT3 protein expression was independently associated with LNM and served as a biomarker for predicting cancer recurrence and death. CCT3 promotes LNM in cervical cancer by upregulating the expression and activating the function of the PI3K/AKT signaling pathway, which represents a novel mechanism contributing to tumor recurrence and mortality. CCT3 may serve as a valuable prognostic biomarker and potential therapeutic target.