Keratin 17 drives endometrial cancer aggressiveness via epithelial-mesenchymal transition: a single-cell transcriptomic and integrative bioinformatics study

Abstract Endometrial cancer (EC) is a common gynecological malignancy with increasing incidence, and advanced or recurrent cases have limited treatment options. The role of Keratin 17 (KRT17), a type I intermediate filament protein implicated in tumor progression in other cancers, remains unclear in EC. This study aimed to investigate the expression, prognostic significance, and functional mechanisms of KRT17 in EC. Bioinformatics analysis revealed significant upregulation of KRT17 in EC tissues, with elevated expression strongly correlated with adverse clinical outcomes and reduced overall survival. Single-cell RNA sequencing (scRNA-seq) analysis elucidated the distribution and expression profiles of KRT17 in malignant epithelial cells of endometrial cancer, and differential expression analysis combined with gene set enrichment analysis (GSEA) further confirmed the significant enrichment of KRT17 in the EMT pathway. In vitro functional assays confirmed that stable knockdown of KRT17 significantly inhibited the proliferation, migration, invasion, and spheroid formation of EC cells, and altered the expression of key EMT markers. In vivo animal models demonstrated that KRT17 knockdown effectively suppressed tumor growth and reversed the EMT process. Collectively, KRT17 functions as an oncogene in EC by activating EMT to drive malignant progression, representing a potential therapeutic target.