PTK6 inhibition by tilfrinib hinders the proliferation and migration of ovarian cancer cells

Protein Tyrosine Kinase 6 (PTK6) has been implicated in the progression of multiple malignancies; however, its oncogenic role and therapeutic potential in ovarian cancer (OC) remain incompletely defined. This study systematically investigates the biological function and therapeutic relevance of PTK6 inhibition by tilfrinib in OC. Comprehensive multi-omics analyses were conducted to identify differentially expressed genes (DEGs). PTK6 expression was validated across multiple datasets and correlated with survival, tumor stage, and oncogenic signaling pathways. Functional studies were performed using lentiviral-mediated PTK6 knockdown and pharmacological inhibition with tilfrinib in OC. Cellular proliferation and migration were assessed using CCK-8, EdU incorporation, wound healing, and colony formation assays. Molecular docking analysis was conducted to evaluate the interaction between PTK6 and tilfrinib. PTK6 was significantly upregulated in ovarian cancer, and the high expression of PTK6 was associated with poorer overall survival, disease-specific survival, and progression-free survival. Single-cell transcriptomic analysis revealed that PTK6 expression was predominantly localized to epithelial and malignant cell populations. Functional inhibition of PTK6 markedly suppressed proliferation and migration in Caov-4 and ID8 ovarian cancer cells. ShRNA-mediated PTK6 knockdown significantly impaired the subcutaneous tumorigenic potential of the Caov-4 cells in vivo. Molecular docking demonstrated that tilfrinib forms a stable complex with PTK6, and pharmacological inhibition resulted in dose-dependent suppression of OC cell proliferation. PTK6 promotes ovarian cancer progression by enhancing tumor cell proliferation and migration. Inhibition of PTK6 by tilfrinib represents a promising therapeutic strategy for ovarian cancer.