A study published in Current Molecular Pharmacology identified a mechanism for gastric cancer metastasis involving the long non-coding RNA PVT1 and the translation initiation factor EIF4A1. These elements cooperate to drive metastasis by upregulating STC1 and activating the Notch1 pathway.

PVT1 binds to the N-terminal domain of EIF4A1, which leads to increased expression of the secreted glycoprotein STC1. Elevated STC1 activates the Notch1 signaling pathway and promotes epithelial–mesenchymal transition, consequently enhancing tumor cell migration, invasion, and proliferation.

Researchers employed 4D-DIA quantitative proteomics and mass spectrometry to identify STC1 as a downstream effector of the PVT1/EIF4A1 axis. An immunohistochemical analysis of 183 gastric cancer tissues confirmed that STC1 is upregulated in tumors and correlates with lymph node metastasis, histological type, and tumor stage.

Further experiments in mouse lung metastasis models demonstrated that the co-overexpression of PVT1 and EIF4A1 resulted in the highest levels of STC1 and the greatest number of metastatic lesions. Knocking down STC1 in cells that overexpressed both PVT1 and EIF4A1 reversed pro-migratory and pro-proliferative effects and suppressed the activation of Notch1 and EMT markers.

"Our findings demonstrate that STC1 acts as a critical mediator of the PVT1-EIF4A1 oncogenic axis in gastric cancer," said Dongmei Li, a corresponding author. "Targeting this pathway, particularly STC1 or the PVT1-EIF4A1 interaction, may offer new therapeutic opportunities for patients with aggressive, metastatic gastric cancer."

The study authors state that future research should explore the tumor microenvironment's influence and integrate multi-omics approaches to refine precision treatment strategies. This study identifies a specific molecular pathway involving PVT1, EIF4A1, and STC1 that contributes to the spread of gastric cancer. Understanding this mechanism provides insight into how the disease progresses, and the findings suggest potential targets for therapeutic intervention in metastatic gastric cancer.