Tiam1 Mediated Enhancement of AKT/mTOR and ERK/STAT3 Signaling Promotes Proliferation, Invasion and Migration of Pancreatic Cancer.

Abstract

Objective: To explore the role of Tiam1 in proliferation, invasion, and migration of pancreatic cancer.

Significance: Previous studies have shown that T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1) is involved in multiple tumor progression. However, the role and molecular mechanism of this molecule in pancreatic cancer remain unclear. The aim of this study was to determine the expression level of Tiam1, investigate the underlying molecular mechanism of Tiam1 in pancreatic cancer, and provide reference for the diagnosis and treatment of pancreatic cancer.

Methods: The expression levels of Tiam1 protein in pancreatic cancer tissues and normal pancreatic tissues were investigated using Western blot experiments. We use short interfering RNA creating Tiam1-silenced pancreatic cancer cells. Subsequently, Edu, colony formation, cck-8 cell viability assays, and Transwell migration and invasion assays were performed to explore the biological role of Tiam1 in pancreatic cancer cells. The possible molecular pathways of Tiam1 in pancreatic cancer cells were investigated using Western blot experiments. We use subcutaneous tumorigenesis experiments to explore the role of tiam1 in vivo experiments.

Results: The results showed that the expression of Tiam1 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues. The proliferation, invasion, and migration ability of Tiam1-silenced pancreatic cancer cells was significantly decreased. Tiam1 positively regulates AKT/mTOR and ERK/STAT3 cell signaling pathways. Down-regulation of tiam1 expression slowed the proliferation of subcutaneous tumors.

Conclusions: High expression of Tiam1 in pancreatic cancer promotes pancreatic cancer progression and may be a potential biomarker and therapeutic target for poor prognosis.