TFDP1 transcriptionally activates KIF22 to enhance aggressiveness and stemness in endometrial cancer: implications for prognosis and targeted therapy

Abstract

This study aims to elucidate the role of Kinesin Family Member 22 (KIF22) as a critical regulator of aggressive behavior in endometrial cancer (uterine corpus endometrial carcinoma, UCEC) and to uncover its underlying mechanisms, thereby providing a molecular rationale for future targeted treatment. Bioinformatics analyses were employed to assess KIF22 and TFDP1 expression in UCEC, examining their prognostic value and associations with disease progression. Expression levels were validated in UCEC tissues using qRT-PCR and western blotting. Potential TFDP1 binding sites on the KIF22 promoter were predicted using the JASPAR database and confirmed via dual-luciferase reporter assays. Functional assays, including CCK-8, transwell, and spheroid formation assays, were conducted to evaluate the effects of KIF22 knockdown on UCEC cell behavior. A mouse xenograft model was utilized to investigate the in vivo impact of KIF22 suppression on tumor growth and stemness. KIF22 expression was significantly elevated in UCEC tissues, correlating with reduced overall survival in patients with high KIF22 levels. Overexpression of KIF22 enhanced the proliferation, migration, and sphere formation of UCEC cells. Similarly, high TFDP1 expression was associated with poorer patient outcomes. KIF22 was found to be positively regulated by the TFDP1 transcription factor, which bound to the KIF22 promoter and activated its expression in UCEC cells. In vivo, KIF22 knockdown markedly impeded the tumor formation of cells and reduced stemness marker expression. KIF22, upregulated by TFDP1, enhances UCEC cell aggressiveness and is linked to poor prognosis, highlighting its potential as a target for therapeutic intervention in endometrial cancer.