Fas Signaling Promotes Gastric Cancer Metastasis through STAT3-Dependent Upregulation of Fascin

• Published in: PloS one Vol. 10; no. 5; p. e0125132
• Main Authors: Yang, Yunshan, Zhao, Qiyu, Cai, Zhijian, Cheng, Guoping, Chen, Ming, Wang, Jiaoli, Zhong, Haijun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.05.2015; Public Library of Science (PLoS)
• Subjects: Actin; Aged; Animal tissues; Animals; Apoptosis; Breast cancer; Cancer; Cancer metastasis; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Chemotherapy; Correlation; Correlation analysis; Development and progression; fas Receptor - genetics; fas Receptor - metabolism; Female; Gastric cancer; Gene Knockdown Techniques; Heterografts; Hospitals; Human subjects; Humans; Immunohistochemistry; Kinases; Ligands; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Male; Medical prognosis; Medicine; Metastases; Metastasis; Mice; Mice, Nude; Microfilament Proteins - antagonists & inhibitors; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Middle Aged; Motility; Patients; Physiological aspects; Regulation; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; RNA, Small Interfering - genetics; Rodents; Signal Transduction; Signaling; Stat3 protein; STAT3 Transcription Factor - metabolism; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Surgery; Transcription; Transcription factors; Transducers; Tumors; Up-Regulation; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125132

Fas signaling-activated signal transducers and activators of transcription 3 (STAT3) is required for Fascin upregulation. As an actin-bundling protein, Fascin can mediate gastric cancer (GC) cell migration. Gastric cancer AGS cells were treated with anti-Fas (5 μg/ml) for 2 h, in order to stimulate the activation of the Fas signaling. The in vitro migration of Fas signaling-activated AGS cells was assessed using Transwell chambers. The levels of Fascin and phosphorylated STAT3 were detected by Western blotting analyses. Nude mice were injected intravenously with AGS cells treated with anti-Fas or treated with STAT3 inhibitor without anti-Fas; tumor pulmonary metastases were measured. Fascin protein expression in tumor tissues was detected by immunohistochemistry. The Fas and Fascin mRNA levels in tumor tissues from patients with GC were measured by real-time PCR and their correlation was analyzed. The activation of Fas signaling promoted cell migration and resulted in STAT3-dependent Fascin upregulation in AGS cells. STAT3 enhanced Fascin levels in vivo. Fascin was the mediator of Fas signaling-induced AGS cell migration in vitro and in vivo. Furthermore, there was a positive correlation between Fas and Fascin mRNA levels in tumor tissues from GC patients. Fas signaling promotes GC metastasis through the STAT3/Fascin pathway, which may provide a new target for GC therapy.