| First Author | Winner M | Year | 2007 |
| Journal | Cancer Res | Volume | 67 |
| Issue | 1 | Pages | 186-93 |
| PubMed ID | 17210698 | Mgi Jnum | J:117327 |
| Mgi Id | MGI:3696000 | Doi | 10.1158/0008-5472.CAN-06-3292 |
| Citation | Winner M, et al. (2007) Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Cancer Res 67(1):186-93 |
| abstractText | Low oxygen tension-mediated transcription by hypoxia-inducible factors (HIF) has been reported to facilitate tumor progression, therapeutic resistance, and metastatic adaptation. One previously described target of hypoxia-mediated transcription is the cytokine/growth factor macrophage migration inhibitory factor (MIF). In studies designed to better understand hypoxia-stimulated MIF function, we have discovered that not only is MIF induced by hypoxia in pancreatic adenocarcinoma but MIF is also necessary for maximal hypoxia-induced HIF-1alpha expression. Cells lacking MIF are defective in hypoxia- and prolyl hydroxylase inhibitor-induced HIF-1alpha stabilization and subsequent transcription of glycolytic and angiogenic gene products. Moreover, COP9 signalosome subunit 5 (CSN5), a component of the COP9 signalosome previously reported to functionally interact with MIF, has recently been shown to interact with and stabilize HIF-1alpha. Our results indicate that MIF interacts with CSN5 in pancreatic cancer cells and that MIF-depleted cells display marked defects in hypoxia-induced CSN5/HIF-1alpha interactions. This functional interdependence between HIF-1alpha and MIF may represent an important and previously unrecognized pro-tumorigenic axis. |
