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
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
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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