The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling
| Autor: | Marta Vilalta, Adam J. Krieg, Caiyun G. Li, Eui Jung Moon, Amato J. Giaccia, Jen-Tsan Chi, Edward E. Graves, Jacob G. Kirkland, Stephano S. Mello, Anh N. Diep, Marjan Rafat, Yu Miao, Edward L. LaGory, Laura D. Attardi, Kaushik N. Thakkar, Laura Castellini, Ik Jae Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer microenvironment
STAT3 Transcription Factor 0301 basic medicine Transcription Genetic Science General Physics and Astronomy Breast Neoplasms Article General Biochemistry Genetics and Molecular Biology Metastasis Mice 03 medical and health sciences Breast cancer 0302 clinical medicine Cell Line Tumor medicine Animals Humans MafF Transcription Factor Neoplasm Invasiveness Neoplasm Metastasis STAT3 Fibrosarcoma Cancer Multidisciplinary Oncogene biology Nuclear Proteins Oncogenes General Chemistry Hypoxia-Inducible Factor 1 alpha Subunit Interleukin-11 Prognosis medicine.disease Metastatic breast cancer Cell Hypoxia Gene Expression Regulation Neoplastic Basic-Leucine Zipper Transcription Factors 030104 developmental biology Tumor progression 030220 oncology & carcinogenesis Cancer research biology.protein Female Signal transduction Signal Transduction |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021) Nature Communications |
| DOI: | 10.1038/s41467-021-24631-6 |
| Popis: | 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. Hypoxia plays a critical role in tumor progression including invasion and metastasis. Here, the authors screened several hypoxia inducible genes and identified the oncogenic role of MAFF in breast cancer metastasis and that it activates IL11/STAT3 pathway. |
| Databáze: | OpenAIRE |
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