食管鳞癌组织中干性相关分子Nanog高表达通过激活TGF-β信号通路促进肿瘤侵袭转移
[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].
发表日期:2024 Jun 20
作者:
C Sun, S Zheng, M Li, M Yang, M Qin, Y Xu, W Liang, J Hu, L Wang, F Li, H Zhou, L Yang
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
目的探讨Nanog在食管鳞状细胞癌(ESCC)组织中的表达及其与MMP-2/MMP-9蛋白的调控关系。我们检测了127例食管鳞癌组织和82例癌旁正常组织中Nanog和MMP-2/MMP-9蛋白的表达情况。采用免疫组织化学方法探讨其与患者临床病理参数及预后的相关性。利用GEO数据库分析Nanog等干性相关分子富集的通路,利用TIMER在线工具分析食管癌中TβR1、MMP-2、MMP-9之间的相关性。Nanog与MMP-2/MMP -9蛋白在ESCC组织中显着上调并且呈正相关。它们的表达水平与食管鳞癌的浸润深度和淋巴结转移密切相关,但与年龄、性别或肿瘤分化程度无关。 Nanog和MMP-2/MMP-9高表达的患者生存时间明显缩短。生物信息学分析显示TGF-β信号通路中干性相关分子富集,且MMP-2/MMP-9与TβR1的表达呈正相关。在培养的 ESCC 细胞中,Nanog 敲低显着降低了 TβR1、p-Smad2/3、MMP-2 和 MMP-9 的表达,并强烈抑制细胞迁移。Nanog、MMP-2 和 MMP-9 的高表达,呈正相关,与食管鳞癌的浸润深度、淋巴结转移及预后密切相关。 Nanog通过TGF-β信号通路调节MMP-2/MMP-9蛋白的表达,其高表达促进ESCC细胞的迁移。
To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC).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.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.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.