TIM-3 promotes the metastasis of esophageal squamous cell carcinoma by targeting epithelial-mesenchymal transition via the Akt/GSK-3β/Snail signaling pathway

TIM-3 expression was significantly elevated in esophageal squamous cell carcinoma (ESCC) tissues compared to matched adjacent normal tissues (both P<0.001).

• Higher TIM-3 levels in ESCC are associated with lymph node metastasis (P=0.008), tumor-node-metastasis (TNM) stage (P=0.042), and depth of tumor invasion (P=0.042).
• Increased TIM-3 expression correlates with worse overall survival in ESCC patients (P=0.001).
• Knockdown of TIM-3 in ESCC cell lines significantly inhibits proliferation, migration, and invasion, but does not affect apoptosis.
• Depletion of TIM-3 leads to decreased levels of matrix metalloproteinase (MMP)-9 and increased levels of tissue inhibitor of metalloproteinase (TIMP)-1.
• The reversal of epithelial-mesenchymal transition (EMT) is observed with TIM-3 knockdown, indicated by increased E-cadherin and decreased N-cadherin and vimentin levels.
• TIM-3 depletion suppresses the Akt/GSK-3β/Snail signaling pathway.

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