HIF-1α promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model.

Oncology Letters
Jianning ZhuJinhai Fan

Abstract

Lung is one of the most common sites for bladder cancer to metastasize. Although the involvement of the epithelial-to-mesenchymal transition (EMT) in bladder cancer progression has been established, the mechanism of EMT induction remains unclear. In order to investigate this, T24-parental (P) and T24-lung (L) bladder cancer cells were obtained from primary tumors and lung metastatic sites of an animal model with orthotopic spontaneous metastatic bladder cancer, according to a protocol previously described. Compared with T24-P cells, mesenchymal-like T24-L cells exhibited an increased ability in tumor invasion and metastasis, as well as an increased expression of hypoxia-inducible factor (HIF)-1α, zinc finger E-box-binding homeobox 1 (ZEB1), vimentin and N-cadherin and lower level of cytokeratin 18 were observed. Mechanistically, it was identified that HIF-1α increases ZEB1 expression and subsequently regulates the expression of EMT-related genes in both HIF-1α knocking down by siRNA and gain-in HIF-1α by hypoxia culture cell models. In addition, the expression of HIF-1α and ZEB1 in bladder cancer tissues were increased compared with normal bladder epithelial tissues, as well as significantly increased in the high-grade, invasiv...Continue Reading

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Citations

Apr 24, 2020·Frontiers in Oncology·Shing Yau TamHelen K W Law
Aug 13, 2020·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Jul 10, 2020·International Journal of Molecular Sciences·Fanny BeryKarine Mahéo

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Methods Mentioned

BETA
transfection
immunoprecipitation assay
protein assay
xenograft

Software Mentioned

SPSS

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