Direct regulation of TWIST by HIF-1α promotes metastasis

Muh Hwa Yang, Min Zu Wu, Shih Hwa Chiou, Po Min Chen, Shyue Yih Chang, Chung Ji Liu, Shu Chun Teng, Kou Juey Wu*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

1162 引文 斯高帕斯(Scopus)

摘要

Stabilization of the hypoxia-inducible factor-1α (HIF-1α) transcription complex, caused by intratumoural hypoxia, promotes tumour progression and metastasis, leading to treatment failure and mortality in different types of human cancers. The transcription factor TWIST is a master regulator of gastrulation and mesoderm-specification and was implicated recently as an essential mediator of cancer metastasis. Notably, HIF-1α- and TWIST-null mice show similarities in their phenotypes. Here, we have shown that hypoxia or overexpression of HIF-1α promotes epithelial-mesenchymal transition (EMT) and metastastic phenotypes. We also found that HIF-1 regulates the expression of TWIST by binding directly to the hypoxia-response element (HRE) in the TWIST proximal promoter. However, siRNA-mediated repression of TWIST in HIF-1α-overexpressing or hypoxic cells reversed EMT and metastastic phenotypes. Co-expression of HIF-1α, TWIST and Snail in primary tumours of patients with head and neck cancers correlated with metastasis and the worst prognosis. These results provide evidence of a key signalling pathway involving HIF-1α and TWIST that promotes metastasis in response to intratumoural hypoxia.

原文英語
頁(從 - 到)295-305
頁數11
期刊Nature Cell Biology
10
發行號3
DOIs
出版狀態已出版 - 03 2008
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