Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression
Prostate cancer, the most common malignancy in men, has a relatively favourable prognosis. However, when it spreads to the bone, the survival rate drops dramatically. The development of bone metastases leaves patients with aggressive prostate cancer, the leading cause of death in men. Moreover, bone...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13739 |
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| author | Elisa Carouge Clémence Burnichon Martin Figeac Shéhérazade Sebda Nathalie Vanpouille Audrey Vinchent Marie‐José Truong Martine Duterque‐Coquillaud David Tulasne Anne Chotteau‐Lelièvre |
| author_facet | Elisa Carouge Clémence Burnichon Martin Figeac Shéhérazade Sebda Nathalie Vanpouille Audrey Vinchent Marie‐José Truong Martine Duterque‐Coquillaud David Tulasne Anne Chotteau‐Lelièvre |
| author_sort | Elisa Carouge |
| collection | DOAJ |
| description | Prostate cancer, the most common malignancy in men, has a relatively favourable prognosis. However, when it spreads to the bone, the survival rate drops dramatically. The development of bone metastases leaves patients with aggressive prostate cancer, the leading cause of death in men. Moreover, bone metastases are incurable and very painful. Hepatocyte growth factor receptor (MET) and fusion of genes encoding E26 transformation‐specific (ETS) transcription factors are both involved in the progression of the disease. ETS gene fusions, in particular, have the ability to induce the migratory and invasive properties of prostate cancer cells, whereas MET receptor, through its signalling cascades, is able to activate transcription factor expression. MET signalling and ETS gene fusions are intimately linked to high‐grade prostate cancer. However, the collaboration of these factors in prostate cancer progression has not yet been investigated. Here, we show, using cell models of advanced prostate cancer, that ETS translocation variant 1 (ETV1) and transcriptional regulator ERG (ERG) transcription factors (members of the ETS family) promote tumour properties, and that activation of MET signalling enhances these effects. By using a specific MET tyrosine kinase inhibitor in a humanised hepatocyte growth factor (HGF) mouse model, we also establish that MET activity is required for ETV1/ERG‐mediated tumour growth. Finally, by performing a comparative transcriptomic analysis, we identify target genes that could play a relevant role in these cellular processes. Thus, our results demonstrate for the first time in prostate cancer models a functional interaction between ETS transcription factors (ETV1 and ERG) and MET signalling that confers more aggressive properties and highlight a molecular signature characteristic of this combined action. |
| format | Article |
| id | doaj-art-c7d3e53625bf407f9ba9f1676e644f3d |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-c7d3e53625bf407f9ba9f1676e644f3d2025-02-04T17:30:20ZengWileyMolecular Oncology1574-78911878-02612025-02-0119247449510.1002/1878-0261.13739Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progressionElisa Carouge0Clémence Burnichon1Martin Figeac2Shéhérazade Sebda3Nathalie Vanpouille4Audrey Vinchent5Marie‐José Truong6Martine Duterque‐Coquillaud7David Tulasne8Anne Chotteau‐Lelièvre9UMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUS 41 – UAR 2014 – PLBS Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUS 41 – UAR 2014 – PLBS Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceUMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille FranceProstate cancer, the most common malignancy in men, has a relatively favourable prognosis. However, when it spreads to the bone, the survival rate drops dramatically. The development of bone metastases leaves patients with aggressive prostate cancer, the leading cause of death in men. Moreover, bone metastases are incurable and very painful. Hepatocyte growth factor receptor (MET) and fusion of genes encoding E26 transformation‐specific (ETS) transcription factors are both involved in the progression of the disease. ETS gene fusions, in particular, have the ability to induce the migratory and invasive properties of prostate cancer cells, whereas MET receptor, through its signalling cascades, is able to activate transcription factor expression. MET signalling and ETS gene fusions are intimately linked to high‐grade prostate cancer. However, the collaboration of these factors in prostate cancer progression has not yet been investigated. Here, we show, using cell models of advanced prostate cancer, that ETS translocation variant 1 (ETV1) and transcriptional regulator ERG (ERG) transcription factors (members of the ETS family) promote tumour properties, and that activation of MET signalling enhances these effects. By using a specific MET tyrosine kinase inhibitor in a humanised hepatocyte growth factor (HGF) mouse model, we also establish that MET activity is required for ETV1/ERG‐mediated tumour growth. Finally, by performing a comparative transcriptomic analysis, we identify target genes that could play a relevant role in these cellular processes. Thus, our results demonstrate for the first time in prostate cancer models a functional interaction between ETS transcription factors (ETV1 and ERG) and MET signalling that confers more aggressive properties and highlight a molecular signature characteristic of this combined action.https://doi.org/10.1002/1878-0261.13739CapmatinibETS transcription factorsMET signallingprostate cancertranscriptomic analysis |
| spellingShingle | Elisa Carouge Clémence Burnichon Martin Figeac Shéhérazade Sebda Nathalie Vanpouille Audrey Vinchent Marie‐José Truong Martine Duterque‐Coquillaud David Tulasne Anne Chotteau‐Lelièvre Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression Molecular Oncology Capmatinib ETS transcription factors MET signalling prostate cancer transcriptomic analysis |
| title | Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression |
| title_full | Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression |
| title_fullStr | Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression |
| title_full_unstemmed | Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression |
| title_short | Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression |
| title_sort | functional interaction between receptor tyrosine kinase met and ets transcription factors promotes prostate cancer progression |
| topic | Capmatinib ETS transcription factors MET signalling prostate cancer transcriptomic analysis |
| url | https://doi.org/10.1002/1878-0261.13739 |
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