RCN1 couple KIF14 and promotes the malignant progression of cervical cancer via the PI3K-mTOR pathway

Purpose: Cervical cancer ranks as the fourth leading cause of cancer-related mortality among women. While early-stage cases often respond well to therapy, advanced and recurrent disease remains challenging to manage. This study aimed to elucidate the molecular mechanisms driving cervical cancer progression to uncover potential therapeutic targets. Methods: Quantitative proteomic profiling (LC-MS/MS) was performed to compare protein expression patterns between cervical carcinoma and normal cervical tissues. Validation was conducted through immunoblotting, quantitative PCR, and immunohistochemical analyses. Functional characterization of RCN1 in tumor progression was assessed using cellular assays and animal models. To delineate downstream signaling, IP-MS was employed in RCN1-deficient cells, followed by immunoblotting to examine alterations in KIF14 and PI3K-AKT-mTOR pathway components. Results: Elevated RCN1 expression was observed in cervical cancer patients with lymphatic dissemination and disease recurrence, correlating with unfavorable clinical outcomes. Genetic manipulation studies demonstrated RCN1's role in enhancing neoplastic proliferation, motility, and invasive capacity. In vivo experiments confirmed that RCN1 overexpression potentiated pulmonary metastasis. Mechanistically, RCN1 was found to interact with KIF14, a known regulator of AKT phosphorylation, thereby activating the PI3K-AKT-mTOR signaling axis. Conclusion: Our findings identify RCN1 as a clinically significant biomarker associated with aggressive cervical cancer phenotypes. The RCN1-KIF14 interaction promotes oncogenic signaling through PI3K-AKT-mTOR pathway activation, suggesting novel intervention strategies for metastatic cervical carcinoma management.