Research Paper Volume 12, Issue 4 pp 3574—3593

SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway

Shan Tian 1, *, , Pailan Peng 2, *, , Jiao Li 1, , Huan Deng 1, , Na Zhan 3, , Zhi Zeng 3, , Weiguo Dong 1, ,

  • 1 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430061, Hubei Province, China
  • 2 Department of Gastroenterology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
  • 3 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430061, Hubei Province, China
* Equal contribution

received: November 25, 2019 ; accepted: January 22, 2020 ; published: February 24, 2020 ;

https://doi.org/10.18632/aging.102831
How to Cite

Copyright © 2020 Tian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

In this study, we investigated the role of SERPINH1 in gastric cancer (GC) progression. GC patient tissues show significantly higher SERPINH1 mRNA and protein levels than normal gastric mucosal tissues. GC patients with high SERPINH1 expression are associated with lymph node metastasis and poor prognosis. SERPINH1 mRNA levels negatively correlate with E-cadherin mRNA levels and positively correlate with levels of N-cadherin, MMP2, and MMP9 mRNA levels. This suggests SERPINH1 regulates epithelial to mesenchymal transition (EMT). SERPINH1 expression was significantly higher in the HGC-27, AGS, MGC-803, and SGC-7901 GC cell lines than in the GES-1 normal gastric mucosal cell line. In SERPINH1-silenced SGC-7901 cells, survival, colony formation, migration and invasion were all reduced, whereas they were all enhanced in SERPINH1-overexpressing MGC-803 cells. Levels of WNT/β-catenin signaling pathway proteins, including β-catenin, Wnt2, GSK-3β, p-GSK-3β, NF-κB P65, Snail1, Slug and TWIST, were all reduced in SERPINH1-silenced SGC-7901 cells, and increased in the SERPINH1-overexpressing MGC-803 cells. Inhibition of SERPINH1 protein using Co1003 significantly decreased survival, invasion, and migration of GC cells. SERPINH1 thus appears to regulate EMT and GC progression via the Wnt/β-catenin pathway, making SERPINH1 a potential prognostic biomarker and therapeutic target in GC patients.

Abbreviations

GC: Gastric cancer; SERPINH1: Serpin Family H Member 1; HSP47: Heat shock protein 47; EMT: Epithelial-mesenchymal transition; ECM: extracellular matrix; IHC: Immunohistochemistry; DAB: Diaminobenzidine; TCGA: The Cancer Genome Atlas; GEO: Gene expression omnibus; OS: Overall survival; PFS: Progression-free survival.