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Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome

Author

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  • Shin Yoshimoto

    (Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
    CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan)

  • Tze Mun Loo

    (Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
    CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
    Tokyo University of Science, Noda, Chiba 278-8510, Japan)

  • Koji Atarashi

    (Research Center for Allergy and Immunology, RIKEN, Yokohama, Kanagawa 230-0045, Japan
    PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan)

  • Hiroaki Kanda

    (Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan)

  • Seidai Sato

    (Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
    CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan)

  • Seiichi Oyadomari

    (Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan)

  • Yoichiro Iwakura

    (Research Institute for Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan)

  • Kenshiro Oshima

    (Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8561, Japan)

  • Hidetoshi Morita

    (School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa 229-8501, Japan)

  • Masahira Hattori

    (Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8561, Japan)

  • Kenya Honda

    (CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
    Research Center for Allergy and Immunology, RIKEN, Yokohama, Kanagawa 230-0045, Japan)

  • Yuichi Ishikawa

    (Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan)

  • Eiji Hara

    (Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
    CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan)

  • Naoko Ohtani

    (Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
    PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan)

Abstract

Obesity is shown in a mouse model of liver cancer to strongly enhance tumorigenesis; a high fat diet alters the composition of intestinal bacteria, leading to more production of the metabolite DCA which, probably together with other factors, induces senescence and the secretion of various senescence-associated cytokines in hepatic stellate cells, thus promoting cancer.

Suggested Citation

  • Shin Yoshimoto & Tze Mun Loo & Koji Atarashi & Hiroaki Kanda & Seidai Sato & Seiichi Oyadomari & Yoichiro Iwakura & Kenshiro Oshima & Hidetoshi Morita & Masahira Hattori & Kenya Honda & Yuichi Ishikaw, 2013. "Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome," Nature, Nature, vol. 499(7456), pages 97-101, July.
    • Handle: RePEc:nat:nature:v:499:y:2013:i:7456:d:10.1038_nature12347
    DOI: 10.1038/nature12347
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    Citations

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    Cited by:

    1. Nanase Igarashi & Kenichi Miyata & Tze Mun Loo & Masatomo Chiba & Aki Hanyu & Mika Nishio & Hiroko Kawasaki & Hao Zheng & Shinya Toyokuni & Shunsuke Kon & Keiji Moriyama & Yasuyuki Fujita & Akiko Taka, 2022. "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Marjolein Heddes & Baraa Altaha & Yunhui Niu & Sandra Reitmeier & Karin Kleigrewe & Dirk Haller & Silke Kiessling, 2022. "The intestinal clock drives the microbiome to maintain gastrointestinal homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Mariana F. Fernández & Iris Reina-Pérez & Juan Manuel Astorga & Andrea Rodríguez-Carrillo & Julio Plaza-Díaz & Luis Fontana, 2018. "Breast Cancer and Its Relationship with the Microbiota," IJERPH, MDPI, vol. 15(8), pages 1-20, August.
    4. Rana Salam & Alexa Saliou & Franck Bielle & Mathilde Bertrand & Christophe Antoniewski & Catherine Carpentier & Agusti Alentorn & Laurent Capelle & Marc Sanson & Emmanuelle Huillard & Léa Bellenger & , 2023. "Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    5. Tu, Wangshu & Browne, Ryan & Subedi, Sanjeena, 2024. "A mixture of logistic skew-normal multinomial models," Computational Statistics & Data Analysis, Elsevier, vol. 196(C).
    6. Kotaro Soeda & Takayoshi Sasako & Kenichiro Enooku & Naoto Kubota & Naoki Kobayashi & Yoshiko Matsumoto Ikushima & Motoharu Awazawa & Ryotaro Bouchi & Gotaro Toda & Tomoharu Yamada & Takuma Nakatsuka , 2023. "Gut insulin action protects from hepatocarcinogenesis in diabetic mice comorbid with nonalcoholic steatohepatitis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Benjamin Assouline & Rachel Kahn & Lutfi Hodali & Reba Condiotti & Yarden Engel & Ela Elyada & Tzlil Mordechai-Heyn & Jason R. Pitarresi & Dikla Atias & Eliana Steinberg & Tirza Bidany-Mizrahi & Esthe, 2024. "Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8+ T cell activation and limit responsiveness to immunotherapy in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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