2. Academic Validation
  3. PCDHGA9 represses epithelial-mesenchymal transition and metastatic potential in gastric cancer cells by reducing β-catenin transcriptional activity

PCDHGA9 represses epithelial-mesenchymal transition and metastatic potential in gastric cancer cells by reducing β-catenin transcriptional activity

  • Cell Death Dis. 2020 Mar 30;11(3):206. doi: 10.1038/s41419-020-2398-z.
Junyong Weng  # 1 2,  Shanbao Li  # 3,  Hao Lin  # 4,  Haitao Mei 1,  Yang Liu 1,  Chao Xiao 1 5,  Zhonglin Zhu 1 6,  Weiwei Cai 7,  Xusheng Ding 2,  Yushuai Mi 8,  Yugang Wen 9
Affiliations

Affiliations

  • 1 Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080, Shanghai, China.
  • 2 Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China.
  • 3 Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, 201800, Shanghai, China.
  • 4 Department of Medicine II, University Hospital, Liver Centre Munich, LMU, Munich, 80539, Germany.
  • 5 Department of General Surgery, Shanghai Huashan Hospital, Fudan University, 200000, Shanghai, China.
  • 6 Department of General Surgery, Henan Provincial People's Hospital, 450003, Zhengzhou, Henan, China.
  • 7 Department of Medicine, The Third Hospital of Quanzhou, 362000, Quanzhou, China.
  • 8 Department of General Surgery, The Second Hospital of Shandong University, 250033, Jinan, Shandong, China. [email protected].
  • 9 Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 32231199 DOI: 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.

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