DSG3 promotes bladder cancer growth and metastasis via AKT/GSK3β/β-catenin pathway

作者：Tao Wang, An-Qi Du, Yuan Peng, Jianjian Yin, Guoqiang Sun, Yihang Yu, Zhangran Sun, Qi Chang, Kaidi Gong, Shengna Han, Lirong Zhang, Dongkui Song · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06754-2 · 被引用次数：4 · 研究领域：Wnt/β-catenin signaling in development and cancer、Cancer-related gene regulation、Hippo pathway signaling and YAP/TAZ

BACKGROUND: The high metastasis rate is the primary contributor to the high mortality rate associated with muscle-invasive bladder cancer (MIBC). Therefore, elucidating the mechanisms involved and identifying potential therapeutic targets are crucial for improving the overall prognosis of bladder cancer (BLCA). METHODS: We used consensus clustering and differential gene expression analyses to identify the key gene desmoglein 3 (DSG3). Subsequently, we examined the expression of DSG3 in BLCA and its association with the clinical characteristics and prognosis. Comprehensive in vitro and in vivo experiments were conducted to elucidate the functions of DSG3 and the reasons behind the upregulation of DSG3 in BLCA, as well as to investigate the mechanisms by which DSG3 promotes metastasis. RESULTS: DSG3 was markedly upregulated in BLCA, particularly in the basal/squamous (Ba/Sq) subtype. Importantly, elevated DSG3 levels demonstrated a strong association with aggressive tumor behavior and poorer clinical outcomes. Functional experiments revealed that DSG3 knockdown significantly impeded cancer stemness characteristics, epithelial-mesenchymal transition (EMT), migration, and invasion capabilities in vitro, whereas in vivo studies showed marked reductions in tumorigenesis and lung metastasis. Mechanistic investigations indicated that STAT3 transcriptionally activated DSG3 expression in BLCA cells. Downstream pathway analysis further showed that DSG3 promoted AKT phosphorylation, ther...