The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling.

Journal Article (Journal Article)

Hypoxia 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.

Full Text

Duke Authors

Cited Authors

  • Moon, EJ; Mello, SS; Li, CG; Chi, J-T; Thakkar, K; Kirkland, JG; Lagory, EL; Lee, IJ; Diep, AN; Miao, Y; Rafat, M; Vilalta, M; Castellini, L; Krieg, AJ; Graves, EE; Attardi, LD; Giaccia, AJ

Published Date

  • July 14, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 4308 -

PubMed ID

  • 34262028

Pubmed Central ID

  • PMC8280233

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-24631-6


  • eng

Conference Location

  • England