YY1 inhibits the migration and invasion of pancreatic ductal adenocarcinoma by downregulating the FER/STAT3/MMP2 signaling pathway.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and a high mortality rate. The transcription factor YY1 acts as an inhibitor of many types of tumors. We found that YY1 knockdown promoted the invasion and migration of PANC-1 and BxPC-3 cells; FER knockdown partially restored the promotion of pancreatic cancer caused by YY1 knockdown. In vivo experiments yielded the same results. According to luciferase reporter gene, electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays, YY1 directly binds to the FER promoter region. Moreover, higher level FER expression results in a worse TNM stage and prognosis for patients with PDAC. Furthermore, by downregulating FER, YY1 inhibits the formation of the STAT3-MMP2 complex, thereby suppressing expression of MMP2 and ultimately inhibiting the migration and invasion of pancreatic cancer. Our study demonstrates that the YY1/FER/STAT3/MMP2 axis is associated with the progression of pancreatic cancer and may provide a new therapeutic target for the treatment of pancreatic cancer.

• Authors: Qun Chen, Jing-Jing Zhang, Wan-Li Ge, Lei Chen, Hao Yuan, Ling-Dong Meng, Xu-Min Huang, Peng Shen, Yi Miao, Kui-Rong Jiang
• Journal: Cancer letters (Cancer Lett) Vol. 463 Pg. 37-49 (Oct 28 2019) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 31404611 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• STAT3 Transcription Factor
• STAT3 protein, human
• YY1 Transcription Factor
• YY1 protein, human
• proto-oncogene protein c-fes-fps
• Protein-Tyrosine Kinases
• Matrix Metalloproteinase 2

Topics

• Adenocarcinoma (metabolism, physiopathology)
• Carcinoma, Pancreatic Ductal (metabolism, physiopathology)
• Cell Movement (physiology)
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Humans
• Matrix Metalloproteinase 2 (physiology)
• Neoplasm Invasiveness (physiopathology)
• Protein-Tyrosine Kinases (metabolism, physiology)
• STAT3 Transcription Factor (physiology)
• Signal Transduction (physiology)
• Tumor Cells, Cultured
• YY1 Transcription Factor (physiology)