| First Author | Yang MH | Year | 2008 |
| Journal | Nat Cell Biol | Volume | 10 |
| Issue | 3 | Pages | 295-305 |
| PubMed ID | 18297062 | Mgi Jnum | J:175157 |
| Mgi Id | MGI:5284765 | Doi | 10.1038/ncb1691 |
| Citation | Yang MH, et al. (2008) Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 10(3):295-305 |
| abstractText | Stabilization of the hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha- and TWIST-null mice show similarities in their phenotypes. Here, we have shown that hypoxia or overexpression of HIF-1alpha 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-1alpha-overexpressing or hypoxic cells reversed EMT and metastastic phenotypes. Co-expression of HIF-1alpha, 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-1alpha and TWIST that promotes metastasis in response to intratumoural hypoxia. |
