PCDHGA9 represses epithelial-mesenchymal transition and metastatic potential in gastric cancer cells by reducing β-catenin transcriptional activity
Open Access
- 30 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (3), 1-18
- https://doi.org/10.1038/s41419-020-2398-z
Abstract
Gastric cancer (GC) has a high mortality rate, and metastasis is the main reason for treatment failure. It is important to study the mechanism of tumour invasion and metastasis based on the regulation of key genes. In a previous study comparing the expression differences between GES-1 and SGC-7901 cells, PCDHGA9 was selected for further research. In vitro and in vivo experiments showed that PCDHGA9 inhibited invasion and metastasis. A cluster analysis suggested that PCDHGA9 inhibited epithelial-mesenchymal transition (EMT) through the Wnt/β-catenin and TGF-β pathways. Laser confocal techniques and western blotting revealed that PCDHGA9 inhibited the nuclear translocation of β-catenin, regulated T cell factor (TCF)/ /lymphoid enhancer factor (LEF) transcriptional activity, directly impacted the signal transmission of the TGF-β/Smad2/3 pathway, strengthened the adhesion complex, weakened the effects of TGF-β, and blocked the activation of the Wnt pathway. In addition, PCDHGA9 expression was regulated by methylation, which was closely related to poor clinical prognosis. The aim of this study was to elucidate the molecular mechanism by which PCDHGA9 inhibits EMT and metastasis in GC to provide a new theoretical basis for identifying GC metastasis and a new target for improving the outcome of metastatic GC.Keywords
Funding Information
- Science and Technology Commission of Shanghai Municipality (17ZR1422800)
- National Natural Science Foundation of China (81972215, 81802420)
This publication has 31 references indexed in Scilit:
- Wnt Signaling through Inhibition of β-Catenin Degradation in an Intact Axin1 ComplexCell, 2012
- RACK1 Suppresses Gastric Tumorigenesis by Stabilizing the β-Catenin Destruction ComplexGastroenterology, 2012
- Cdx2 Controls Expression of the Protocadherin Mucdhl, an Inhibitor of Growth and β-Catenin Activity in Colon Cancer CellsGastroenterology, 2012
- Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathwaysOncogene, 2012
- A Perspective on Cancer Cell MetastasisScience, 2011
- β-catenin–mediated Wnt signaling regulates neurogenesis in the ventral telencephalonNature Neuroscience, 2008
- Coordinated Functions of E-Cadherin and Transforming Growth Factor β Receptor II In vitro and In vivoCancer Research, 2006
- Thermodynamics of β-Catenin-Ligand InteractionsPublished by Elsevier BV ,2006
- Distinct mechanisms of TGF- 1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesisJCI Insight, 2005
- Crystal Structure of a β-Catenin/Tcf ComplexCell, 2000