CELL INTELLIGENCE · 肿瘤细胞治疗研究

Chronic myeloid leukemia (CML) is driven by uncontrolled myeloid proliferation, yet underlying molecular mechanisms remain incompletely understood. This study investigated the pan-cancer expression profile of N-cadherin (CDH2) and its potential role in suppressing proliferation in K562 CML cells, with an exploratory focus on the GSK3β/β-catenin axis. We combined in silico analyses (TCGA/GEO datasets) with functional assays in K562 cells. CDH2 expression was assessed across 31 cancer types. In K562 cells, we evaluated the effects of CDH2 overexpression on proliferation, cell cycle, apoptosis, and several proteins within the β-catenin/GSK3β network. CDH2 was significantly upregulated in 18 malignancies and downregulated in 10. It was associated with adverse overall survival in five solid tumors but favorable in KIRC. In acute myeloid leukemia (AML), higher CDH2 expression correlated with poor-prognosis cytogenetic risk (P = 0.008). CDH2 expression also correlated with macrophage/NK cell infiltration in some solid tumors. In K562 cells, CDH2 overexpression suppressed proliferation, induced cell cycle arrest and early apoptosis. This was accompanied by increased total β-catenin protein but a reduced nuclear-to-cytoplasmic β-catenin ratio, without consistent changes in canonical Wnt target gene expression. Notably, the GSK3 inhibitor CHIR-99,021 reversed the anti-proliferative effect of CDH2, whereas the β-catenin degrader MSAB did not rescue it. CDH2 exhibits context-dependent expression across malignancies. In K562 CML cells, CDH2 overexpression suppresses proliferation through a GSK3β-sensitive mechanism. However, the precise molecular mechanism remains unresolved. Our findings suggest that targeting GSK3β may represent a therapeutic vulnerability in this model.