A study recently published in Current Molecular Pharmacology has uncovered a novel mechanism by which the long non‑coding RNA PVT1 and the translation initiation factor EIF4A1 cooperate to drive gastric cancer metastasis. The researchers show that PVT1 binds to the N‑terminal domain of EIF4A1, and this interaction leads to increased expression of the secreted glycoprotein STC1. Elevated STC1, in turn, activates the Notch1 signalling pathway and promotes epithelial–mesenchymal transition, significantly enhancing tumour cell migration, invasion and proliferation.
Using 4D‑DIA quantitative proteomics and mass spectrometry, the team identified STC1 as a key downstream effector of the PVT1/EIF4A1 axis. Immunohistochemical analysis of 183 gastric cancer tissues confirmed that STC1 is markedly upregulated in tumours and correlates with lymph node metastasis, histological type and tumour stage. In mouse lung metastasis models, co‑overexpression of PVT1 and EIF4A1 produced the highest STC1 levels and the greatest number of 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 the activation of Notch1 and EMT markers was suppressed.
"Our findings demonstrate that STC1 acts as a critical mediator of the PVT1‑EIF4A1 oncogenic axis in gastric cancer," said corresponding author Dr. Dongmei Li from Shihezi University. "Targeting this pathway, particularly STC1 or the PVT1‑EIF4A1 interaction, may offer new therapeutic opportunities for patients with aggressive, metastatic gastric cancer." The study also highlights the potential of STC1 as an auxiliary diagnostic marker. The authors note that future research should explore the tumour microenvironment's influence and integrate multi‑omics approaches to refine precision treatment strategies.
