Abstract
AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.
Funder
U.S. Department of Health & Human Services | NIH | National Cancer Institute
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference66 articles.
1. Brown, J. M. & Giaccia, A. J. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 58, 1408–1416 (1998).
2. Moon, E. J., Brizel, D. M., Chi, J. T. & Dewhirst, M. W. The potential role of intrinsic hypoxia markers as prognostic variables in cancer. Antioxid. Redox Signal 9, 1237–1294 (2007).
3. Wilson, W. R. & Hay, M. P. Targeting hypoxia in cancer therapy. Nat. Rev. Cancer 11, 393–410 (2011).
4. Semenza, G. L. Molecular mechanisms mediating metastasis of hypoxic breast cancer cells. Trends Mol. Med. 18, 534–543 (2012).
5. LaGory, E. L. & Giaccia, A. J. The ever-expanding role of HIF in tumour and stromal biology. Nat. Cell Biol. 18, 356–365 (2016).
Cited by
60 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献