The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells
Open Access
- 10 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 13 (4), e13162
- https://doi.org/10.15252/emmm.202013162
Abstract
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 HIF1α‐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.Keywords
Funding Information
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (#310030_184673 20)
- Novartis
- Krebsliga Beider Basel
This publication has 75 references indexed in Scilit:
- NFIB is a governor of epithelial–melanocyte stem cell behaviour in a shared nicheNature, 2013
- Evolution of the cancer genomeNature Reviews Genetics, 2012
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroupsNature, 2012
- Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomesNature Medicine, 2011
- Integrative genomics viewerNature Biotechnology, 2011
- Transposon-based screens for cancer gene discovery in mouse modelsSeminars in Cancer Biology, 2010
- An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patientsBreast Cancer Research and Treatment, 2009
- Transposon-mediated genome manipulation in vertebratesNature Methods, 2009