In a recently published study, Current molecular pharmacology discovered a novel mechanism by which long non-coding RNA PVT1 and translation initiation factor EIF4A1 cooperate to promote gastric cancer metastasis. Researchers showed that PVT1 binds to the N-terminal domain of EIF4A1 and that this interaction leads to increased expression of the secreted glycoprotein STC1. Elevated STC1 activates the Notch1 signaling pathway, promotes epithelial-mesenchymal transition, and significantly promotes tumor cell migration, invasion, and proliferation.
Using 4D‑DIA quantitative proteomics and mass spectrometry, the research team identified STC1 as a key downstream effector of the PVT1/EIF4A1 axis. Immunohistochemical analysis of 183 gastric cancer tissues confirmed that STC1 was significantly upregulated within tumors and correlated with lymph node metastasis, histology, and tumor stage. In a mouse lung metastasis model, simultaneous overexpression of PVT1 and EIF4A1 produced the highest STC1 levels and the most metastatic lesions. When the researchers knocked down STC1 in cells overexpressing both PVT1 and EIF4A1, the pro-migratory and pro-proliferative effects were reversed and activation of Notch1 and EMT markers was suppressed.
Our findings indicate that STC1 functions as an important mediator of the PVT1‑EIF4A1 oncogenic axis in gastric cancer. Targeting this pathway, particularly STC1 or the PVT1-EIF4A1 interaction, may provide new therapeutic opportunities for patients with aggressive metastatic gastric cancer. ”
Dr. Dongmei Li, corresponding author, Shihezi University
This study also highlights the potential of STC1 as an auxiliary diagnostic marker. The authors note that future studies should investigate the influence of the tumor microenvironment and integrate multi-omics approaches to refine precision treatment strategies.
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Reference magazines:
Cao Cao, D. Others. (2026). PVT1&EIF4A1 promotes metastasis by regulating Notch-1 signaling pathway through STC-1 in gastric cancer. Current molecular pharmacology. DOI: 10.1016/j.cmp.2026.02.003. https://www.sciencedirect.com/science/article/pii/S1874467226000036?via%3Dihub
