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Transcriptomic Profiling Identifies GPNMB as a Key Driver of Gastric Cancer Aggressiveness

GSE330529 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/05/17 Platform GPL24676
Summary
We aimed to define the role of GPNMB in gastric cancer (GC) progression and its underlying mechanisms. Stable GPNMB-knockdown/overexpression GC cell models were established, and transcriptomic profiling identified the cAMP signaling pathway as a key downstream effector. GPNMB silencing significantly inhibited GC cell proliferation, invasion, induced G1 arrest and apoptosis, while overexpression activated the cAMP/PKA/CREB axis to upregulate c-Myc, Cyclin D1 and EMT markers, which was reversed by the PKA inhibitor H-89. GPNMB also promoted an immunosuppressive microenvironment via IL-6 and TGF-β upregulation and accelerated xenograft tumor growth. Our findings identify GPNMB as a critical driver of GC malignancy through the cAMP/PKA/CREB axis, representing a promising therapeutic target.
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Also filed as BioProject PRJNA1464558 and SRA study SRP699282. Searching any of these in the dataset finder brings you back here.

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