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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Nature
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39743589/ |
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| author | Doglioni, Ginevra Fernández-García, Juan Igelmann, Sebastian Altea-Manzano, Patricia Blomme, Arnaud La Rovere, Rita Liu, Xiao-Zheng Liu, Yawen Tricot, Tine Nobis, Max An, Ning Leclercq, Marine El Kharraz, Sarah Karras, Panagiotis Hsieh, Yu-Heng Solari, Fiorella A Martins Nascentes Melo, Luiza Allies, Gabrielle Scopelliti, Annalisa Rossi, Matteo Vermeire, Ines Broekaert, Dorien Ferreira Campos, Ana Margarida Neven, Patrick Maetens, Marion Van Baelen, Karen Alkan, H Furkan Planque, Mélanie Floris, Giuseppe Sickmann, Albert Tasdogan, Alpaslan Marine, Jean-Christophe Scheele, Colinda L G J Desmedt, Christine Bultynck, Geert Close, Pierre Fendt, Sarah-Maria |
| author_facet | Doglioni, Ginevra Fernández-García, Juan Igelmann, Sebastian Altea-Manzano, Patricia Blomme, Arnaud La Rovere, Rita Liu, Xiao-Zheng Liu, Yawen Tricot, Tine Nobis, Max An, Ning Leclercq, Marine El Kharraz, Sarah Karras, Panagiotis Hsieh, Yu-Heng Solari, Fiorella A Martins Nascentes Melo, Luiza Allies, Gabrielle Scopelliti, Annalisa Rossi, Matteo Vermeire, Ines Broekaert, Dorien Ferreira Campos, Ana Margarida Neven, Patrick Maetens, Marion Van Baelen, Karen Alkan, H Furkan Planque, Mélanie Floris, Giuseppe Sickmann, Albert Tasdogan, Alpaslan Marine, Jean-Christophe Scheele, Colinda L G J Desmedt, Christine Bultynck, Geert Close, Pierre Fendt, Sarah-Maria Doglioni, Ginevra Fernández-García, Juan Igelmann, Sebastian Altea-Manzano, Patricia Blomme, Arnaud La Rovere, Rita Liu, Xiao-Zheng Liu, Yawen Tricot, Tine Nobis, Max An, Ning Leclercq, Marine El Kharraz, Sarah Karras, Panagiotis Hsieh, Yu-Heng Solari, Fiorella A Martins Nascentes Melo, Luiza Allies, Gabrielle Scopelliti, Annalisa Rossi, Matteo Vermeire, Ines Broekaert, Dorien Ferreira Campos, Ana Margarida Neven, Patrick Maetens, Marion Van Baelen, Karen Alkan, H Furkan Planque, Mélanie Floris, Giuseppe Sickmann, Albert Tasdogan, Alpaslan Marine, Jean-Christophe Scheele, Colinda L G J Desmedt, Christine Bultynck, Geert Close, Pierre Fendt, Sarah-Maria |
| collection | PubMed - marine biology |
| contents | Aspartate signalling drives lung metastasis via alternative translation. Doglioni, Ginevra Fernández-García, Juan Igelmann, Sebastian Altea-Manzano, Patricia Blomme, Arnaud La Rovere, Rita Liu, Xiao-Zheng Liu, Yawen Tricot, Tine Nobis, Max An, Ning Leclercq, Marine El Kharraz, Sarah Karras, Panagiotis Hsieh, Yu-Heng Solari, Fiorella A Martins Nascentes Melo, Luiza Allies, Gabrielle Scopelliti, Annalisa Rossi, Matteo Vermeire, Ines Broekaert, Dorien Ferreira Campos, Ana Margarida Neven, Patrick Maetens, Marion Van Baelen, Karen Alkan, H Furkan Planque, Mélanie Floris, Giuseppe Sickmann, Albert Tasdogan, Alpaslan Marine, Jean-Christophe Scheele, Colinda L G J Desmedt, Christine Bultynck, Geert Close, Pierre Fendt, Sarah-Maria Lung Neoplasms Animals Female Mice Humans Signal Transduction Aspartic Acid Protein Biosynthesis Breast Neoplasms Lung Receptors, N-Methyl-D-Aspartate Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Male Extracellular Fluid Lung metastases occur in up to 54% of patients with metastatic tumours. Contributing factors to this high frequency include the physical properties of the pulmonary system and a less oxidative environment that may favour the survival of cancer cells. Moreover, secreted factors from primary tumours alter immune cells and the extracellular matrix of the lung, creating a permissive pre-metastatic environment primed for the arriving cancer cells. Nutrients are also primed during pre-metastatic niche formation. Yet, whether and how nutrients available in organs in which tumours metastasize confer cancer cells with aggressive traits is mostly undefined. Here we found that pulmonary aspartate triggers a cellular signalling cascade in disseminated cancer cells, resulting in a translational programme that boosts aggressiveness of lung metastases. Specifically, we observe that patients and mice with breast cancer have high concentrations of aspartate in their lung interstitial fluid. This extracellular aspartate activates the ionotropic N-methyl-D-aspartate receptor in cancer cells, which promotes CREB-dependent expression of deoxyhypusine hydroxylase (DOHH). DOHH is essential for hypusination, a post-translational modification that is required for the activity of the non-classical translation initiation factor eIF5A. In turn, a translational programme with TGFβ signalling as a central hub promotes collagen synthesis in lung-disseminated breast cancer cells. We detected key proteins of this mechanism in lung metastases from patients with breast cancer. In summary, we found that aspartate, a classical biosynthesis metabolite, functions in the lung environment as an extracellular signalling molecule to promote aggressiveness of metastases. |
| format | Artículo científico |
| id | pubmed_39743589 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Nature |
| record_format | pubmed |
| spellingShingle | Aspartate signalling drives lung metastasis via alternative translation. Doglioni, Ginevra Fernández-García, Juan Igelmann, Sebastian Altea-Manzano, Patricia Blomme, Arnaud La Rovere, Rita Liu, Xiao-Zheng Liu, Yawen Tricot, Tine Nobis, Max An, Ning Leclercq, Marine El Kharraz, Sarah Karras, Panagiotis Hsieh, Yu-Heng Solari, Fiorella A Martins Nascentes Melo, Luiza Allies, Gabrielle Scopelliti, Annalisa Rossi, Matteo Vermeire, Ines Broekaert, Dorien Ferreira Campos, Ana Margarida Neven, Patrick Maetens, Marion Van Baelen, Karen Alkan, H Furkan Planque, Mélanie Floris, Giuseppe Sickmann, Albert Tasdogan, Alpaslan Marine, Jean-Christophe Scheele, Colinda L G J Desmedt, Christine Bultynck, Geert Close, Pierre Fendt, Sarah-Maria Lung Neoplasms Animals Female Mice Humans Signal Transduction Aspartic Acid Protein Biosynthesis Breast Neoplasms Lung Receptors, N-Methyl-D-Aspartate Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Male Extracellular Fluid Aspartate signalling drives lung metastasis via alternative translation. Doglioni, Ginevra Fernández-García, Juan Igelmann, Sebastian Altea-Manzano, Patricia Blomme, Arnaud La Rovere, Rita Liu, Xiao-Zheng Liu, Yawen Tricot, Tine Nobis, Max An, Ning Leclercq, Marine El Kharraz, Sarah Karras, Panagiotis Hsieh, Yu-Heng Solari, Fiorella A Martins Nascentes Melo, Luiza Allies, Gabrielle Scopelliti, Annalisa Rossi, Matteo Vermeire, Ines Broekaert, Dorien Ferreira Campos, Ana Margarida Neven, Patrick Maetens, Marion Van Baelen, Karen Alkan, H Furkan Planque, Mélanie Floris, Giuseppe Sickmann, Albert Tasdogan, Alpaslan Marine, Jean-Christophe Scheele, Colinda L G J Desmedt, Christine Bultynck, Geert Close, Pierre Fendt, Sarah-Maria Lung Neoplasms Animals Female Mice Humans Signal Transduction Aspartic Acid Protein Biosynthesis Breast Neoplasms Lung Receptors, N-Methyl-D-Aspartate Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Male Extracellular Fluid Lung metastases occur in up to 54% of patients with metastatic tumours. Contributing factors to this high frequency include the physical properties of the pulmonary system and a less oxidative environment that may favour the survival of cancer cells. Moreover, secreted factors from primary tumours alter immune cells and the extracellular matrix of the lung, creating a permissive pre-metastatic environment primed for the arriving cancer cells. Nutrients are also primed during pre-metastatic niche formation. Yet, whether and how nutrients available in organs in which tumours metastasize confer cancer cells with aggressive traits is mostly undefined. Here we found that pulmonary aspartate triggers a cellular signalling cascade in disseminated cancer cells, resulting in a translational programme that boosts aggressiveness of lung metastases. Specifically, we observe that patients and mice with breast cancer have high concentrations of aspartate in their lung interstitial fluid. This extracellular aspartate activates the ionotropic N-methyl-D-aspartate receptor in cancer cells, which promotes CREB-dependent expression of deoxyhypusine hydroxylase (DOHH). DOHH is essential for hypusination, a post-translational modification that is required for the activity of the non-classical translation initiation factor eIF5A. In turn, a translational programme with TGFβ signalling as a central hub promotes collagen synthesis in lung-disseminated breast cancer cells. We detected key proteins of this mechanism in lung metastases from patients with breast cancer. In summary, we found that aspartate, a classical biosynthesis metabolite, functions in the lung environment as an extracellular signalling molecule to promote aggressiveness of metastases. |
| title | Aspartate signalling drives lung metastasis via alternative translation. |
| topic | Lung Neoplasms Animals Female Mice Humans Signal Transduction Aspartic Acid Protein Biosynthesis Breast Neoplasms Lung Receptors, N-Methyl-D-Aspartate Cell Line, Tumor Cyclic AMP Response Element-Binding Protein Male Extracellular Fluid |
| url | https://pubmed.ncbi.nlm.nih.gov/39743589/ |