HIF-1α stimulates the progression of oesophageal squamous cell carcinoma by activating the Wnt/β-catenin signalling pathway
| العنوان: | HIF-1α stimulates the progression of oesophageal squamous cell carcinoma by activating the Wnt/β-catenin signalling pathway |
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| المؤلفون: | Kang Tang, Takeshi Toyozumi, Kentaro Murakami, Haruhito Sakata, Masayuki Kano, Satoshi Endo, Yasunori Matsumoto, Hiroshi Suito, Masahiko Takahashi, Nobufumi Sekino, Ryota Otsuka, Kazuya Kinoshita, Soichiro Hirasawa, Jie Hu, Masaya Uesato, Koichi Hayano, Hisahiro Matsubara |
| المصدر: | Br J Cancer |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Esophageal Neoplasms, Oncology, Drug Resistance, Neoplasm, Cell Line, Tumor, Humans, Esophageal Squamous Cell Carcinoma, Fluorouracil, Hypoxia-Inducible Factor 1, alpha Subunit, Wnt Signaling Pathway, Article, beta Catenin, Cell Proliferation |
| الوصف: | BACKGROUND: This study aimed to clarify the significance of the crosstalk between hypoxia-inducible factor-1α (HIF-1α) and the Wnt/β-catenin pathway in oesophageal squamous cell carcinoma (ESCC). METHODS: The oncogenic role of HIF-1α in ESCC was investigated using in vitro and in vivo assays. The clinicopathological significance of HIF-1α, β-catenin and TCF4/TCF7L2 in ESCC were evaluated using quantitative real-time PCR and immunohistochemistry. RESULTS: The expression level of HIF-1α, β-catenin, and TCF4/TCF7L2 in T.Tn and TE1 cell lines were elevated under hypoxia in vitro. HIF-1α knockdown suppressed proliferation, migration/invasion and epithelial–mesenchymal transition (EMT) progression, induced G0/G1 cell cycle arrest, promoted apoptosis and inhibited 5-fluorouracil chemoresistance in vitro. In vivo assays showed that HIF-1α is essential in maintaining tumour growth, angiogenesis, and 5-fluorouracil chemoresistance. Mechanically, we identified the complex between HIF-1α and β-catenin, HIF-1α can directly bind to the promoter region of TCF4/TCF7L2. The mRNA level of HIF-1α, β-catenin and TCF4/TCF7L2 were increased in ESCC tumour tissues compared to the corresponding non-tumour tissues. High levels of HIF-1α and TCF4/TCF7L2 expression were correlated with aggressive phenotypes and poor prognosis in ESCC patients. CONCLUSIONS: HIF-1α serves as an oncogenic transcriptional factor in ESCC, probably by directly targeting TCF4/TCF7L2 and activating the Wnt/β-catenin pathway. |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e56b13713b835ffac7b81cf4478e8a37 https://doi.org/10.1038/s41416-022-01825-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e56b13713b835ffac7b81cf4478e8a37 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15321827 00070920 |
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