期刊
EMBO MOLECULAR MEDICINE
卷 13, 期 4, 页码 -出版社
WILEY
DOI: 10.15252/emmm.202013162
关键词
Breast cancer; ERO1A; metastasis; NFIB; VEGFA
资金
- Genomics Core Facility at FMI
- BSSE-ETHZ
- Swiss National Science Foundation [310030_184673 20]
- Swiss Initiative for Systems Biology-SystemsX
- European Research Council (ERC) [694033 STEM-BCPC]
- Novartis
- Krebsliga Beider Basel
- Swiss Cancer League
- Swiss Personalized Health Network (Swiss Personalized Oncology driver project)
- Department of Surgery of the University Hospital Basel
- Swiss National Science Foundation (SNF) [310030_184673] Funding Source: Swiss National Science Foundation (SNF)
NFIB is a transcription factor that plays a crucial role in promoting primary mammary tumor growth and lung metastatic colonization by increasing the expression of ERO1A. Its high expression is associated with poor prognosis in basal-like breast cancer patients.
Metastasis is the main cause of deaths related to solid cancers. Active transcriptional programmes are known to regulate the metastatic cascade but the molecular determinants of metastatic colonization remain elusive. Using an inducible piggyBac (PB) transposon mutagenesis screen, we have shown that overexpression of the transcription factor nuclear factor IB (NFIB) alone is sufficient to enhance primary mammary tumour growth and lung metastatic colonization. Mechanistically and functionally, NFIB directly increases expression of the oxidoreductase ERO1A, which enhances HIF1 alpha-VEGFA-mediated angiogenesis and colonization, the last and fatal step of the metastatic cascade. NFIB is thus clinically relevant: it is preferentially expressed in the poor-prognostic group of basal-like breast cancers, and high expression of the NFIB/ERO1A/VEGFA pathway correlates with reduced breast cancer patient survival.
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