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Crypt stem cells as the cells-of-origin of intestinal cancer

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  • Nick Barker

    (Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht)

  • Rachel A. Ridgway

    (Beatson Institute for Cancer Research)

  • Johan H. van Es

    (Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht)

  • Marc van de Wetering

    (Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht)

  • Harry Begthel

    (Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht)

  • Maaike van den Born

    (Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht)

  • Esther Danenberg

    (Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht)

  • Alan R. Clarke

    (Cardiff School of Biosciences)

  • Owen J. Sansom

    (Beatson Institute for Cancer Research)

  • Hans Clevers

    (Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht)

Abstract

Intestinal cancer: stem-cell destinies Inappropriate activation of the Wnt signalling pathway in intestinal stem cells causes them to become cancerous. Two papers in this issue help identify the cell type at the root of this cancer, which should in turn aid therapeutic design. Zhu et al. report that prominin 1, a surface protein found on both normal stem cells and cancer stem cells, is a marker for stem cells that are prone to neoplastic transformation. Barker et al. show that in cells expressing Lgr5, previously identified as a marker for intestinal stem cells, activation of Wnt signalling is sufficient to initiate tumour formation.

Suggested Citation

  • Nick Barker & Rachel A. Ridgway & Johan H. van Es & Marc van de Wetering & Harry Begthel & Maaike van den Born & Esther Danenberg & Alan R. Clarke & Owen J. Sansom & Hans Clevers, 2009. "Crypt stem cells as the cells-of-origin of intestinal cancer," Nature, Nature, vol. 457(7229), pages 608-611, January.
    • Handle: RePEc:nat:nature:v:457:y:2009:i:7229:d:10.1038_nature07602
    DOI: 10.1038/nature07602
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    Citations

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    Cited by:

    1. Kazuki Nakai & Hancheng Lin & Shotaro Yamano & Shinya Tanaka & Sho Kitamoto & Hitoshi Saitoh & Kenta Sakuma & Junpei Kurauchi & Eilma Akter & Masamitsu Konno & Kojiro Ishibashi & Ryo Kamata & Akihiro , 2023. "Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-κB-MMP21 pathway," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Sefora Conti & Valeria Venturini & Adrià Cañellas-Socias & Carme Cortina & Juan F. Abenza & Camille Stephan-Otto Attolini & Emily Middendorp Guerra & Catherine K. Xu & Jia Hui Li & Leone Rossetti & Gi, 2024. "Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Alfredo Erazo-Oliveras & Mónica Muñoz-Vega & Mohamed Mlih & Venkataramana Thiriveedi & Michael L. Salinas & Jaileen M. Rivera-Rodríguez & Eunjoo Kim & Rachel C. Wright & Xiaoli Wang & Kerstin K. Landr, 2023. "Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    4. Ewart Kuijk & Onno Kranenburg & Edwin Cuppen & Arne Van Hoeck, 2022. "Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Anup Dewanji & Jihyoun Jeon & Rafael Meza & E Georg Luebeck, 2011. "Number and Size Distribution of Colorectal Adenomas under the Multistage Clonal Expansion Model of Cancer," PLOS Computational Biology, Public Library of Science, vol. 7(10), pages 1-10, October.
    6. Shamir Montazid & Sheila Bandyopadhyay & Daniel W. Hart & Nan Gao & Brian Johnson & Sri G. Thrumurthy & Dustin J. Penn & Bettina Wernisch & Mukesh Bansal & Philipp M. Altrock & Fabian Rost & Patrycja , 2023. "Adult stem cell activity in naked mole rats for long-term tissue maintenance," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Lana Kostic & Carly Leung & Katzrin Ahmad Murad & Snezhina Kancheva & Stefano Perna & Bernett Lee & Nick Barker, 2024. "Lgr5 marks stem/progenitor cells contributing to epithelial and muscle development in the mouse esophagus," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Carlos Sebastian & Christina Ferrer & Maria Serra & Jee-Eun Choi & Nadia Ducano & Alessia Mira & Manasvi S. Shah & Sylwia A. Stopka & Andrew J. Perciaccante & Claudio Isella & Daniel Moya-Rull & Maria, 2022. "A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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