TGF-β promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways

摘要

Transforming growth factor-β (TGF-β) is involved in actin cytoskeleton reorganization and tumor pro-gression. Fascin1, an actin-binding protein, increases cell invasiveness and motility in various transformed cells. To determine whether fascin1 is an important mediator of the tumor response to TGF-β, we applied the small interfering RNA (siRNA) technique to silence fascinl in gastric cancer (GC) cells MKN45. Results showed that the effects of TGF-β1 on GC cells invasion and metastasis were mediated by tumor production of fascinl; furthermore, it was found that TGF-β1-induced fascin1 expression was suppressed by the specific inhibitors of JNK and ERK pathways, SP6001125 and PD98059, respectively, but not by tran-sient transfection of Smad2 and Smad4 siRNA. Our data for the first time demonstrated that fascinl is an important mediator of TGF-β1-induced invasion and metastasis of GC cells, which involves JNK and ERK signaling pathways.