This study focuses on the function and molecular mechanisms of the tyrosine kinase non-receptor 2 (TNK2) in esophageal squamous cell carcinoma (ESCC). In this study, using ESCC as a model, techniques such as Western Blot, immunoprecipitation (IP), Transwell assay, and immunofluorescence staining, combined with lentiviral transfection experiments, were employed to analyze the molecular regulatory mechanism of TNK2. Analysis revealed a marked increase in TNK2 expression levels in clinical ESCC specimens and established ESCC cell lines. TNK2 promoted epithelial-mesenchymal transition (EMT), proliferation, and invasion of ESCC cells. Functional experiments demonstrate that TNK2 promotes EMT, proliferation, and invasive capacity in ESCC cells. Mechanistically, TNK2 interacts with AKT and promotes its phosphorylation, which in turn inhibits the ubiquitination and proteasomal degradation of FOXO1, ultimately leading to increased FOXO1 protein expression. This study reveals that TNK2 enhances FOXO1 expression via the AKT signaling axis, thereby driving ESCC malignant progression. Genipin targets TNK2 to inhibit the progression of ESCC. It provides new insights into the pathogenesis of ESCC and theoretical basis for positioning TNK2 gene as a potential therapeutic target.
Zhou et al. (Wed,) studied this question.