当前位置： SCI文献检索 > Oncology Letters期刊下所有文献 > HIF-1α promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model.

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

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, invasive and metastatic bladder cancer tissues compared with low-grade, superficial and non-metastatic bladder cancer tissues by using immune-histochemical staining assay. Notably, the protein level of HIF-1α was positively associated with that of ZEB1 in bladder cancer tissues. Results from the present study indicate that HIF-1α promotes ZEB1 expression and EMT in the T24-L human bladder cancer lung metastasis animal model, suggesting that HIF-1α serves an important function in the metastasis of bladder cancer, and HIF-1α and ZEB1 may be potential targets for inhibiting bladder metastasis in the future.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Zhu J,Huang Z,Zhang M,Wang W,Liang H,Zeng J,Wu K,Wang X,Hsieh JT,Guo P,Fan J

doi

10.3892/ol.2018.7764

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

3482-3489

issue

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-7764

journal_volume

pub_type

杂志文章

在线工具

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