The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells

The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells

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 s...

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Bibliographic Details
Main Authors: Federica Zilli, Pedro Marques Ramos, Priska Auf der Maur, Charly Jehanno, Atul Sethi, Marie‐May Coissieux, Tobias Eichlisberger, Loïc Sauteur, Adelin Rouchon, Laura Bonapace, Joana Pinto Couto, Roland Rad, Michael Rugaard Jensen, Andrea Banfi, Michael B Stadler, Mohamed Bentires‐Alj
Format: Article
Language:English
Published: Springer Nature 2021-04-01
Series:EMBO Molecular Medicine
Subjects:
Breast cancer
ERO1A
metastasis
NFIB
VEGFA
Online Access:https://doi.org/10.15252/emmm.202013162
Description
Summary: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.
ISSN:1757-4676
1757-4684

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