title: Signal transducer and activator of transcription 3 signaling upregulates fascin via nuclear factor-κB in gastric cancer: Implications in cell invasion and migration.
abstract: Fascin protein plays important roles in tumor metastasis and is prognostically relevant to human gastric cancer (GC). However, its role in the development and progression of GC has not been comprehensively investigated. In the present study, results revealed that upregulation of fascin by interleukin-6 promotes GC cell migration and invasion in a signal transducer and activator of transcription 3 (STAT3)-dependent manner in MKN45 cells. Furthermore, STAT3 directly regulated fascin expression and nuclear factor-κB (NF-κB) bound to the fascin promoter in a STAT3-dependent and Notch-independent manner. Therefore, results demonstrate that STAT3 and NF-κB are required for upregulation of fascin and for cell migration and invasion in MKN45 cells. Effects of the treatments on cell signaling were detected by qPCR, western blot analysis and chromatin immunoprecipitation (ChIP) assay. Cell migration and invasion were analyzed using in vitro scratch wound healing assay, transwell and Matrigel assays, and xenograft model. In addition, the STAT3-NF-κB-fascin signaling axis is identified as a therapeutic target for blocking GC cell invasion and migration.
authors: Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, P.R. China.
authors: Jun
authors: J
authors: Yao
authors: Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, P.R. China ; Insitute of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors: Cui-Juan
authors: CJ
authors: Qian
authors: Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou, Zhejiang 318000, P.R. China.
authors: Bei
authors: B
authors: Ye
authors: Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, P.R. China.
authors: Zhi-Qiang
authors: ZQ
authors: Zhao
authors: Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, P.R. China.
authors: Jie
authors: J
authors: Wei
authors: Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, P.R. China.
authors: Yong
authors: Y
authors: Liang
authors: Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou, Zhejiang 318000, P.R. China.
authors: Xin
authors: X
authors: Zhang
keywords: Notch; fascin; gastric cancer; metastasis; nuclear factor-κB; signal transducer and activator of transcription 3