Abstract
As a nuclear transport receptor, KPNB1 transport proteins from cytoplasm into nucleus, performing a vital function in intracellular traffic. The aberrant upregulation of KPNB1 has been associated with various malignancies and transformed cells, where it is indispensable for cellular proliferation and survival. Transcription factors like E2F1 possess a nuclear localization motif that triggers the expression of a range of crucial factors during tumorigenesis. This investigation explores the influence of KPNB1 in cervical cancer (CC) cell metastasis and proliferation through the modulation of E2F1 nuclear import. Overexpression of KPNB1 was consistently detected in cervical carcinoma tissues and associated cell lines, with notably higher levels observed relative to normal cervical mucosa. Functional studies demonstrated that KPNB1 silencing induced a marked attenuation in the invasive, migratory, and proliferative capacities of HeLa and SiHa cells. Furthermore, inhibition of KPNB1 hindered the nuclear translocation of E2F1. Importantly, the application of ARQ171, a small-molecule compound that functionally elevates E2F1 expression, negated partially the suppressive effects of KPNB1 on migration, invasion, and growth of CC cells via elevating the total amount of nuclear E2F1, suggesting that E2F1 mediates the oncogenic role of KPNB1 in CC progression. The research findings highlight the potential utility of targeting KPNB1-E2F1 axis as an innovative treatment modality, underscoring its promise as a novel approach in cervical cancer treatment.