SERPINH1 Regulates EMT and Gastric Cancer Metastasis Via the Wnt/β-catenin Signaling Pathway

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Feb 25

PMID 32091407

Citations 103

Authors

Shan Tian

Pailan Peng

Jiao Li

Huan Deng

Na Zhan

Zhi Zeng

Weiguo Dong

Affiliations

Soon will be listed here.

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.

Citing Articles

TMEM97 governs partial epithelial-mesenchymal transition of retinal pigment epithelial cells via the CTNND2-ADAM10 axis.

Li J, Nagasaka Y, Shen H, Zhou X, Ma J, Trevisan-Silva D Mol Ther Nucleic Acids. 2025; 36(1):102460.

PMID: 39995975 PMC: 11848774. DOI: 10.1016/j.omtn.2025.102460.

Acetyltransferase NAT10 promotes gastric cancer progression by regulating the Wnt/β-catenin signaling pathway and enhances chemotherapy resistance.

Chen Y, Yang J, Du Y, Yan Z, Gao J, Zhang H Discov Oncol. 2025; 16(1):173.

PMID: 39945932 PMC: 11825422. DOI: 10.1007/s12672-025-01917-5.

Deciphering the generation of heterogeneity in esophageal squamous cell carcinoma metastasis via single-cell multiomics analysis.

Sheng K, Chen J, Xu R, Sun H, Liu R, Wang Y J Transl Med. 2025; 23(1):148.

PMID: 39905485 PMC: 11792320. DOI: 10.1186/s12967-025-06154-6.

Machine learning-random forest model was used to construct gene signature associated with cuproptosis to predict the prognosis of gastric cancer.

Liu X, Tao P, Su H, Li Y Sci Rep. 2025; 15(1):4170.

PMID: 39905263 PMC: 11794614. DOI: 10.1038/s41598-025-88812-9.

New insights into Notch signaling as a crucial pathway of pancreatic cancer stem cell behavior by chrysin-polylactic acid-based nanocomposite.

Ragab E, El Gamal D, El-Najjar F, Elkomy H, Ragab M, Elantary M Discov Oncol. 2025; 16(1):107.

PMID: 39891818 PMC: 11787125. DOI: 10.1007/s12672-025-01846-3.

References

Gao Y, Chen Z, Wang R, Tan X, Huang C, Chen G . LXRα Promotes the Differentiation of Human Gastric Cancer Cells through Inactivation of Wnt/β-catenin Signaling. J Cancer. 2019; 10(1):156-167. PMC: 6329868. DOI: 10.7150/jca.28600. View

Aguilera-Montilla N, Bailon E, Uceda-Castro R, Ugarte-Berzal E, Santos A, Gutierrez-Gonzalez A . MMP-9 affects gene expression in chronic lymphocytic leukemia revealing CD99 as an MMP-9 target and a novel partner in malignant cell migration/arrest. Oncogene. 2019; 38(23):4605-4619. DOI: 10.1038/s41388-019-0744-3. View

Ito S, Ogawa K, Takeuchi K, Takagi M, Yoshida M, Hirokawa T . A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis. J Biol Chem. 2017; 292(49):20076-20085. PMC: 5723997. DOI: 10.1074/jbc.M117.815936. View

Zhao D, Jiang X, Yao C, Zhang L, Liu H, Xia H . Heat shock protein 47 regulated by miR-29a to enhance glioma tumor growth and invasion. J Neurooncol. 2014; 118(1):39-47. DOI: 10.1007/s11060-014-1412-7. View

Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2011; 127(12):2893-917. DOI: 10.1002/ijc.25516. View

Zhu J, Xiong G, Fu H, Evers B, Zhou B, Xu R . Chaperone Hsp47 Drives Malignant Growth and Invasion by Modulating an ECM Gene Network. Cancer Res. 2015; 75(8):1580-91. PMC: 4401637. DOI: 10.1158/0008-5472.CAN-14-1027. View

Yamamoto N, Kinoshita T, Nohata N, Yoshino H, Itesako T, Fujimura L . Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma. Int J Oncol. 2013; 43(6):1855-63. PMC: 3834344. DOI: 10.3892/ijo.2013.2145. View

Hagiwara S, Iwasaka H, Matsumoto S, Noguchi T . Antisense oligonucleotide inhibition of heat shock protein (HSP) 47 improves bleomycin-induced pulmonary fibrosis in rats. Respir Res. 2007; 8:37. PMC: 1876458. DOI: 10.1186/1465-9921-8-37. View

Chen C, Shi C, Huang X, Zheng J, Zhu Z, Li Q . Molecular Profiles and Metastasis Markers in Chinese Patients with Gastric Carcinoma. Sci Rep. 2019; 9(1):13995. PMC: 6769015. DOI: 10.1038/s41598-019-50171-7. View

10.

Ji C, Yang L, Yi W, Xiang D, Wang Y, Zhou Z . Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway. Oncogene. 2018; 37(29):3953-3966. PMC: 6053357. DOI: 10.1038/s41388-018-0226-z. View

11.

Mori K, Toiyama Y, Otake K, Fujikawa H, Saigusa S, Hiro J . Proteomics analysis of differential protein expression identifies heat shock protein 47 as a predictive marker for lymph node metastasis in patients with colorectal cancer. Int J Cancer. 2016; 140(6):1425-1435. DOI: 10.1002/ijc.30557. View

12.

Nakayama S, Mukae H, Sakamoto N, Kakugawa T, Yoshioka S, Soda H . Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts. Life Sci. 2007; 82(3-4):210-7. DOI: 10.1016/j.lfs.2007.11.003. View

13.

Huang L, Zhai E, Cai S, Lin Y, Liao J, Jin H . Stress-inducible Protein-1 promotes metastasis of gastric cancer via Wnt/β-catenin signaling pathway. J Exp Clin Cancer Res. 2018; 37(1):6. PMC: 5769340. DOI: 10.1186/s13046-018-0676-8. View

14.

Yao H, Zhao Y, He Y, Huang D, Wang W . Knockdown of AGGF1 inhibits the invasion and migration of gastric cancer via epithelial-mesenchymal transition through Wnt/β-catenin pathway. Cancer Cell Int. 2019; 19:41. PMC: 6391764. DOI: 10.1186/s12935-019-0765-6. View

15.

Sakai S, Ohhata T, Kitagawa K, Uchida C, Aoshima T, Niida H . Long Noncoding RNA Acts as a Smad3 Cofactor to Facilitate TGFβ/Smad Signaling and Promote Epithelial-Mesenchymal Transition. Cancer Res. 2019; 79(11):2821-2838. DOI: 10.1158/0008-5472.CAN-18-3210. View

16.

Wang R, Sun Y, Yu W, Yan Y, Qiao M, Jiang R . Downregulation of miRNA-214 in cancer-associated fibroblasts contributes to migration and invasion of gastric cancer cells through targeting FGF9 and inducing EMT. J Exp Clin Cancer Res. 2019; 38(1):20. PMC: 6334467. DOI: 10.1186/s13046-018-0995-9. View

17.

Hiew M, Cheng H, Huang C, Chong K, Cheong S, Choo K . Incomplete cellular reprogramming of colorectal cancer cells elicits an epithelial/mesenchymal hybrid phenotype. J Biomed Sci. 2018; 25(1):57. PMC: 6052640. DOI: 10.1186/s12929-018-0461-1. View

18.

Zhao Y, Zhong S, Zhang S, Bi J, Xiao Z, Wang S . UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer. Cancer Cell Int. 2019; 19:126. PMC: 6511126. DOI: 10.1186/s12935-019-0848-4. View

19.

Zheng S, Yang L, Dai Y, Jiang L, Wei Y, Wen H . Screening and Survival Analysis of Hub Genes in Gastric Cancer Based on Bioinformatics. J Comput Biol. 2019; 26(11):1316-1325. DOI: 10.1089/cmb.2019.0119. View

20.

Zhang J, Chen Z, Chen D, Tian X, Wang C, Zhou Z . LINC01410-miR-532-NCF2-NF-kB feedback loop promotes gastric cancer angiogenesis and metastasis. Oncogene. 2018; 37(20):2660-2675. PMC: 5955863. DOI: 10.1038/s41388-018-0162-y. View