High MIG-6 expression promotes tumor proliferation and metastasis of gastric cancer

TL;DR

High levels of MIG-6 in gastric cancer are linked to faster tumor growth and worse patient survival, suggesting it could be a new target for treatment.

Contribution

This study reveals a novel role of MIG-6 in promoting gastric cancer progression through EGFR/AKT signaling.

Findings

MIG-6 is overexpressed in gastric cancer tissues and cells.

Reducing MIG-6 lowers tumor growth and metastasis in vitro.

MIG-6 promotes epithelial-mesenchymal transition and MMP-9 expression.

Abstract

Background: Mitogen-inducible gene-6 (MIG-6) is a feedback inhibitor that targets activated epidermal growth factor receptor (EGFR) and suppresses tumor growth fueled by constitutively activated EGFR. Nevertheless, the action mechanism of MIG-6 in gastric cancer (GC) remains to be elucidated.

Methods: Western blotting, fluorescence quantitative PCR, and immunohistochemistry were performed to detect the expression of MIG-6 in GC cell lines and tissues. Public databases were used to analyze MIG-6 in patients with GC. Furthermore, the GC cell lines were selected for the knockdown and overexpression of MIG-6.

Results: Bioinformatics and histological analyses showed that MIG-6 was elevated in human GC tissues and cells. The Kaplan-Meier plotter showed that patients with elevated MIG-6 expression had significantly shorter survival. Furthermore, small interference RNA-mediated reduction of MIG-6 expression decreased EGFR/AKT signaling, as well as the proliferation and metastasis of human GC cells in vitro, whereas its overexpression increased these actions. Also, MIG-6 overexpression promoted the epithelial-mesenchymal transition of GC cells as well as the expression of the migration-associated protein matrix metalloproteinase-9 in vitro.

Conclusion: These results suggest that MIG-6 can serve as a new prognostic biomarker or potential therapeutic target for the identification of patients with poor survival.

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