HSP90/PUS7/THUMPD1 promotes metastasis and cisplatin resistance in gastric cancer cells.

The metastasis and chemotherapy resistance of gastric cancer significantly contribute to treatment failure and mortality. Based on previous studies, we hypothesized that Heat Shock Protein 90 (HSP90) interacts with and upregulates Pseudouridine Synthase 7 (PUS7), which in turn promotes THUMP Domain Containing 1 (THUMPD1) expression, driving gastric cancer progression and drug resistance. Differential gene expression analysis revealed that HSP90, PUS7, and THUMPD1 are overexpressed in multiple tumor types and positively correlate with tumor mutational burden (TMB) and microsatellite instability (MSI). Mechanistically, HSP90 interacts with PUS7 to regulate THUMPD1 expression, enhancing tumor cell proliferation, migration, epithelial-mesenchymal transition (EMT), angiogenesis, and cisplatin resistance. Functional inhibition of HSP90 and THUMPD1 suppressed these oncogenic processes, while PUS7 overexpression exacerbated them. These findings highlight the HSP90/PUS7/THUMPD1 axis as a critical regulator of gastric cancer progression and a potential therapeutic target.