NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K/AKT/GSK signal pathway

Pancreatic cancer (PC) is a continuously high lethal disease, and the tumour microenvironment plays a pivotal role during PC progression. Herein, we focus on that the Nerve growth factor (NGF)/Tropomyosin-related kinase A (TrkA), in pancreatic stellate cells-pancreatic cancer cells (PSCs-PC cells) co-culture system, influences PC proliferation and invasion. The model of PC cells and PSCs was directly co-cultured in a no-touch manner, using the Transwell as the co-culture system. NGF and TrkA expression was measured in cultured system by real-time PCR, immunofluorescence, Western blotting analysis or ELISA. Small interfering RNA transfection was used to regulate the expression of TrkA in PC cells. The promotion of cancer invasion was investigated using Matrigel Transwell assay. In our study, NGF/TrkA is overexpressed in PSCs-PC cells co-culture system and promotes the invasion and proliferation of PC cells. And the epithelial-mesenchymal transition-related genes are influenced by si-TrkA. What's more, NGF/TrkA regulates the PC cell proliferation and invasion via activation of PI3K/AKT/GSK signalling. The present study demonstrated NGF/TrkA promoted the PC cell proliferation and invasion in the co-culture system by the activation of the PI3K/AKT/GSK signal cascade, providing a potential therapeutic target for PC patients.