HIF-1α promotes the stemness of oesophageal squamous cell carcinoma by activating the Wnt/β-catenin pathway

HIF-1α promotes the stemness of oesophageal squamous cell carcinoma by activating the Wnt/β-catenin pathway
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HIF-1α通过激活Wnt/β-catenin通路促进食管鳞状细胞癌的干细胞性

DOI:
10.3892/or.2019.7203
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发表时间:
2019-08-01
期刊:
影响因子:
4.2
通讯作者:
Ren, Xian-Qing
Ren, Xian-Qing
中科院分区:
医学3区
文献类型:
--
作者:
Lv, Zhuan;Liu, Rui-Dong;Ren, Xian-Qing

文献摘要

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缺氧诱导因子1 α(HIF-1 α)是大多数癌症类型预后不良的标志物,并且已被揭示对于维持癌症干细胞(CSC)至关重要。在本研究中,确定了低氧条件下HIF-1 α和CSC相关基因的表达上调。稳定敲低HIF-1 α可显著抑制食管鳞状细胞癌(ESCC)细胞增殖、迁移和肿瘤生长。先前的研究表明,Wnt/β-catenin通路可能在CSC的维持和进展中起关键作用。因此,还揭示了稳定敲除HIF-1 α减少了球体细胞的形成、CSC相关基因和Wnt/β-连环蛋白途径相关靶基因的表达以及Wnt/β-连环蛋白途径的活性。总之,本研究结果表明HIF-1 α可能通过激活Wnt/β-catenin通路调节ESCC的干性。
Hypoxia-inducible-factor 1 alpha (HIF-1 alpha) is a marker for poor prognosis in the majority of the cancer types, and it has been revealed to be essential for maintaining cancer stem cells (CSCs). In the present study, it was determined that the expression of HIF-1 alpha and CSC-related genes under hypoxic conditions was upregulated. Stable knockdown of HIF-1 alpha significantly inhibited cell proliferation, migration and tumour growth in vivo in oesophageal squamous cell carcinoma (ESCC). A previous study revealed that the Wnt/beta-catenin pathway may play a key role in maintenance and progression of CSCs. Therefore, it was also revealed that stable knockdown of HIF-1 alpha reduced the formation of spheroid body cells, the expression of CSC-related genes and Wnt/beta-catenin pathway-related target genes, as well as the activity of the Wnt/beta-catenin pathway. Collectively, the present results indicated that HIF-1 alpha may regulate the stemness of ESCC by activating the Wnt/beta-catenin pathway.