High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF-β signaling pathway
10.12122/j.issn.1673-4254.2024.06.23
- VernacularTitle:干性相关分子Nanog在食管鳞状细胞癌组织中高表达并促进食管鳞癌细胞的侵袭转移:基于激活TGF-β信号通路
- Author:
Chang SUN
1
;
Shiyao ZHENG
;
Mei LI
;
Ming YANG
;
Mengyuan QIN
;
Yuan XU
;
Weihua LIANG
;
Jianmin HU
;
Lianghai WANG
;
Feng LI
;
Hong ZHOU
;
Lan YANG
Author Information
1. 石河子大学医学院病理系//石河子大学第一附属医院病理科,新疆维吾尔自治区 石河子 832000
- Keywords:
esophageal squamous cell carcinoma;
Nanog;
MMP-2/MMP-9;
infiltration and metastasis;
survival analysis
- From:
Journal of Southern Medical University
2024;44(6):1209-1216
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.