Downregulation of stromal syntenin sustains AML development
Abstract The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute mye...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-10-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202317570 |
| _version_ | 1826990710785572864 |
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| author | Raphael Leblanc Rania Ghossoub Armelle Goubard Rémy Castellano Joanna Fares Luc Camoin Stephane Audebert Marielle Balzano Berna Bou‐Tayeh Cyril Fauriat Norbert Vey Sylvain Garciaz Jean‐Paul Borg Yves Collette Michel Aurrand‐Lions Guido David Pascale Zimmermann |
| author_facet | Raphael Leblanc Rania Ghossoub Armelle Goubard Rémy Castellano Joanna Fares Luc Camoin Stephane Audebert Marielle Balzano Berna Bou‐Tayeh Cyril Fauriat Norbert Vey Sylvain Garciaz Jean‐Paul Borg Yves Collette Michel Aurrand‐Lions Guido David Pascale Zimmermann |
| author_sort | Raphael Leblanc |
| collection | DOAJ |
| description | Abstract The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC). Stromal syntenin deficiency, in turn, generates a pro‐tumoral microenvironment. From serial transplantations in mice and co‐culture experiments, we conclude that syntenin‐deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro‐tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, which in trans stimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML–stroma crosstalk and unsuspected tumor‐suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy. |
| first_indexed | 2024-03-07T16:38:16Z |
| format | Article |
| id | doaj.art-5e8657f967514eacb630da97c26abd79 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T08:24:35Z |
| publishDate | 2023-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-5e8657f967514eacb630da97c26abd792024-11-03T12:38:09ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-10-01151111810.15252/emmm.202317570Downregulation of stromal syntenin sustains AML developmentRaphael Leblanc0Rania Ghossoub1Armelle Goubard2Rémy Castellano3Joanna Fares4Luc Camoin5Stephane Audebert6Marielle Balzano7Berna Bou‐Tayeh8Cyril Fauriat9Norbert Vey10Sylvain Garciaz11Jean‐Paul Borg12Yves Collette13Michel Aurrand‐Lions14Guido David15Pascale Zimmermann16Team Spatio‐Temporal Regulation of Cell Signaling‐Scaffolds and Phosphoinositides, Equipe Labellisée Ligue 2018, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‐Calmettes, Aix‐Marseille Université, Inserm, CNRSTeam Spatio‐Temporal Regulation of Cell Signaling‐Scaffolds and Phosphoinositides, Equipe Labellisée Ligue 2018, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‐Calmettes, Aix‐Marseille Université, Inserm, CNRSTrGET Preclinical Platform, Centre de Recherche en Cancérologie de Marseille, Inserm, CNRS, Aix‐Marseille Université, Institut Paoli‐CalmettesTrGET Preclinical Platform, Centre de Recherche en Cancérologie de Marseille, Inserm, CNRS, Aix‐Marseille Université, Institut Paoli‐CalmettesTeam Spatio‐Temporal Regulation of Cell Signaling‐Scaffolds and Phosphoinositides, Equipe Labellisée Ligue 2018, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‐Calmettes, Aix‐Marseille Université, Inserm, CNRSProteomics and Mass Spectrometry Platform, Centre de Recherche en Cancérologie de Marseille, Aix‐Marseille Université, Inserm, CNRS, Institut Paoli CalmettesProteomics and Mass Spectrometry Platform, Centre de Recherche en Cancérologie de Marseille, Aix‐Marseille Université, Inserm, CNRS, Institut Paoli CalmettesTeam Spatio‐Temporal Regulation of Cell Signaling‐Scaffolds and Phosphoinositides, Equipe Labellisée Ligue 2018, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‐Calmettes, Aix‐Marseille Université, Inserm, CNRSTeam Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille, Aix‐Marseille Université, Inserm, CNRS, Institut Paoli CalmettesTeam Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille, Aix‐Marseille Université, Inserm, CNRS, Institut Paoli CalmettesAix‐Marseille Univ, Inserm, CNRS, Institut Paoli‐Calmettes, CRCMAix‐Marseille Univ, Inserm, CNRS, Institut Paoli‐Calmettes, CRCMProteomics and Mass Spectrometry Platform, Centre de Recherche en Cancérologie de Marseille, Aix‐Marseille Université, Inserm, CNRS, Institut Paoli CalmettesTrGET Preclinical Platform, Centre de Recherche en Cancérologie de Marseille, Inserm, CNRS, Aix‐Marseille Université, Institut Paoli‐CalmettesTeam Leuko/Stromal Interactions in Normal and Pathological Hematopoiesis, Centre de Recherche en Cancérologie de Marseille, Aix‐Marseille Université, Inserm, CNRS, Institut Paoli CalmettesTeam Spatio‐Temporal Regulation of Cell Signaling‐Scaffolds and Phosphoinositides, Equipe Labellisée Ligue 2018, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‐Calmettes, Aix‐Marseille Université, Inserm, CNRSTeam Spatio‐Temporal Regulation of Cell Signaling‐Scaffolds and Phosphoinositides, Equipe Labellisée Ligue 2018, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‐Calmettes, Aix‐Marseille Université, Inserm, CNRSAbstract The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC). Stromal syntenin deficiency, in turn, generates a pro‐tumoral microenvironment. From serial transplantations in mice and co‐culture experiments, we conclude that syntenin‐deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro‐tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, which in trans stimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML–stroma crosstalk and unsuspected tumor‐suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.https://doi.org/10.15252/emmm.202317570cell‐to‐cell communicationsyntenintumor aggressivenesstumor–stroma |
| spellingShingle | Raphael Leblanc Rania Ghossoub Armelle Goubard Rémy Castellano Joanna Fares Luc Camoin Stephane Audebert Marielle Balzano Berna Bou‐Tayeh Cyril Fauriat Norbert Vey Sylvain Garciaz Jean‐Paul Borg Yves Collette Michel Aurrand‐Lions Guido David Pascale Zimmermann Downregulation of stromal syntenin sustains AML development EMBO Molecular Medicine cell‐to‐cell communication syntenin tumor aggressiveness tumor–stroma |
| title | Downregulation of stromal syntenin sustains AML development |
| title_full | Downregulation of stromal syntenin sustains AML development |
| title_fullStr | Downregulation of stromal syntenin sustains AML development |
| title_full_unstemmed | Downregulation of stromal syntenin sustains AML development |
| title_short | Downregulation of stromal syntenin sustains AML development |
| title_sort | downregulation of stromal syntenin sustains aml development |
| topic | cell‐to‐cell communication syntenin tumor aggressiveness tumor–stroma |
| url | https://doi.org/10.15252/emmm.202317570 |
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