The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34262028.
- Also identified by DOI 10.1038/s41467-021-24631-6 and PMC identifier 8280233.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Breast Neoplasms
- Hypoxia-Inducible Factor 1, alpha Subunit
- Interleukin-11
- MafF Transcription Factor
- Nuclear Proteins
- STAT3 Transcription Factor