Open AccessThe NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells
Author(s) -
Zilli Federica,
Marques Ramos Pedro,
Auf der Maur Priska,
Jehanno Charly,
Sethi Atul,
Coissieux MarieMay,
Eichlisberger Tobias,
Sauteur Loïc,
Rouchon Adelin,
Bonapace Laura,
Pinto Couto Joana,
Rad Roland,
Jensen Michael Rugaard,
Banfi Andrea,
Stadler Michael B,
BentiresAlj Mohamed
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202013162
Subject(s) - cancer research , colonization , breast cancer , metastatic breast cancer , medicine , cancer , biology , microbiology and biotechnology
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.