A study published in Current Molecular Pharmacology uncovers a new mechanism by which the long non-coding RNA PVT1 and the translation initiation factor EIF4A1 cooperate to drive metastasis in gastric cancer, according to findings released on June 25. The researchers said that PVT1 binds to the N-terminal domain of EIF4A1, resulting in increased expression of the secreted glycoprotein STC1. Elevated STC1 activates the Notch1 signalling pathway and promotes epithelial–mesenchymal transition, leading to enhanced tumour cell migration, invasion, and proliferation.
The research team used 4D-DIA quantitative proteomics and mass spectrometry to identify STC1 as a key downstream effector of the PVT1/EIF4A1 axis. Immunohistochemical analysis of 183 gastric cancer tissues confirmed that STC1 is significantly 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 both the highest levels of STC1 and the greatest number of metastatic lesions. The study found that when 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," the authors said.
The authors also highlight "the potential of STC1 as an auxiliary diagnostic marker." They say future research should explore how the tumour microenvironment influences these processes, as well as integrate multi-omics approaches for more precise treatment strategies.
