JNK-dependent intestinal barrier failure disrupts host-microbe homeostasis during tumorigenesis

• Verfasst von: Zhou, Jun [VerfasserIn]
• Verfasst von: Boutros, Michael [VerfasserIn]
• Titel: JNK-dependent intestinal barrier failure disrupts host-microbe homeostasis during tumorigenesis
• Verf.angabe: Jun Zhou and Michael Boutros
• E-Jahr: 2020
• Jahr: April 10, 2020
• Umfang: 12 S.
• Fussnoten: Gesehen am 04.06.2020
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2020
• Band/Heft Quelle: 117(2020), 17, Seite 9401-9412
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1913976117
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cells
• Sach-SW: drosophila
• Sach-SW: Drosophila
• Sach-SW: dysbiosis
• Sach-SW: epithelial barrier defects
• Sach-SW: expression
• Sach-SW: growth
• Sach-SW: gut immunity
• Sach-SW: host-microbe homeostasis
• Sach-SW: immune-responses
• Sach-SW: insights
• Sach-SW: jnk
• Sach-SW: midgut
• Sach-SW: protein
• Sach-SW: stem cells
• K10plus-PPN: 1699772843

Abstract

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.