JNK-dependent intestinal barrier failure disrupts host-microbe homeostasis during tumorigenesis
In all animals, the intestinal epithelium forms a tight barrier to the environment. The epithelium regulates the absorption of nutrients, mounts immune responses, and prevents systemic infections. Here, we investigate the consequences of tumorigenesis on the microbiome using a Drosophila intestinal...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 10, 2020
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| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2020, Jahrgang: 117, Heft: 17, Pages: 9401-9412 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1913976117 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1913976117
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| Verfasserangaben: | Jun Zhou and Michael Boutros |
| Zusammenfassung: | In all animals, the intestinal epithelium forms a tight barrier to the environment. The epithelium regulates the absorption of nutrients, mounts immune responses, and prevents systemic infections. Here, we investigate the consequences of tumorigenesis on the microbiome using a Drosophila intestinal tumor model. We show that upon loss of BMP signaling, tumors lead to aberrant activation of JNK/Mmp2 signaling, followed by intestinal barrier dysfunction and commensal imbalance. In turn, the dysbiotic microbiome triggers a regenerative response and stimulates tumor growth. We find that inhibiting JNK signaling or depletion of the microbiome restores barrier function of the intestinal epithelium, leading to a reestablishment of host-microbe homeostasis, and organismic lifespan extension. Our experiments identify a JNK-dependent feedback amplification loop between intestinal tumors and the microbiome. They also highlight the importance of controlling the activity level of JNK signaling to maintain epithelial barrier function and host-microbe homeostasis. |
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| Beschreibung: | Gesehen am 04.06.2020 |
| Beschreibung: | Online Resource |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1913976117 |