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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-03-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202013162 |
| _version_ | 1827045110575005696 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Federica Zilli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:52:37Z |
| format | Article |
| id | doaj.art-42ad8c50455f42c9bfe8d2e92e8ddc15 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:20:32Z |
| publishDate | 2021-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-42ad8c50455f42c9bfe8d2e92e8ddc152024-10-28T08:48:53ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-03-0113411910.15252/emmm.202013162The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cellsFederica Zilli0Pedro Marques Ramos1Priska Auf der Maur2Charly Jehanno3Atul Sethi4Marie‐May Coissieux5Tobias Eichlisberger6Loïc Sauteur7Adelin Rouchon8Laura Bonapace9Joana Pinto Couto10Roland Rad11Michael Rugaard Jensen12Andrea Banfi13Michael B Stadler14Mohamed Bentires‐Alj15Department of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselFriedrich Miescher Institute for Biomedical ResearchDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselFriedrich Miescher Institute for Biomedical ResearchDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselNovartis Institutes for Biomedical ResearchDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselDepartment of Medicine II, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics, Center for Translational Cancer Research (TranslaTUM), Technische Universität MünchenNovartis Institutes for Biomedical ResearchDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselFriedrich Miescher Institute for Biomedical ResearchDepartment of Biomedicine, Department of Surgery, University Hospital Basel, University of BaselAbstract 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.https://doi.org/10.15252/emmm.202013162Breast cancerERO1AmetastasisNFIBVEGFA |
| spellingShingle | 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 The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells EMBO Molecular Medicine Breast cancer ERO1A metastasis NFIB VEGFA |
| title | The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells |
| title_full | The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells |
| title_fullStr | The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells |
| title_full_unstemmed | The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells |
| title_short | The NFIB‐ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells |
| title_sort | nfib ero1a axis promotes breast cancer metastatic colonization of disseminated tumour cells |
| topic | Breast cancer ERO1A metastasis NFIB VEGFA |
| url | https://doi.org/10.15252/emmm.202013162 |
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