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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Fas signaling promotes GC metastasis through the STAT3/Fascin pathway, which may provide a new target for GC therapy.

• Authors: Yunshan Yang, Qiyu Zhao, Zhijian Cai, Guoping Cheng, Ming Chen, Jiaoli Wang, Haijun Zhong
• Journal: PloS one (PLoS One) Vol. 10 Issue 5 Pg. e0125132 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25992623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• FAS protein, human
• Microfilament Proteins
• RNA, Messenger
• RNA, Neoplasm
• RNA, Small Interfering
• STAT3 Transcription Factor
• STAT3 protein, human
• fas Receptor
• fascin

Topics

• Aged
• Animals
• Carrier Proteins (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Female
• Gene Knockdown Techniques
• Heterografts
• Humans
• Lung Neoplasms (genetics, metabolism, secondary)
• Male
• Mice
• Mice, Nude
• Microfilament Proteins (antagonists & inhibitors, genetics, metabolism)
• Middle Aged
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• RNA, Small Interfering (genetics)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• Stomach Neoplasms (genetics, metabolism)
• Up-Regulation
• fas Receptor (genetics, metabolism)