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Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells

Author

Listed:
  • Johan H. van Es

    (Netherlands Institute for Developmental Biology)

  • Marielle E. van Gijn

    (Netherlands Institute for Developmental Biology)

  • Orbicia Riccio

    (Ludwig Institute for Cancer Research)

  • Maaike van den Born

    (Netherlands Institute for Developmental Biology)

  • Marc Vooijs

    (Netherlands Institute for Developmental Biology)

  • Harry Begthel

    (Netherlands Institute for Developmental Biology)

  • Miranda Cozijnsen

    (Netherlands Institute for Developmental Biology)

  • Sylvie Robine

    (Institut Curie-CNRS-UMR)

  • Doug J. Winton

    (Cambridge Institute for Medical Research, Addenbrooke's Hospital)

  • Freddy Radtke

    (Ludwig Institute for Cancer Research)

  • Hans Clevers

    (Netherlands Institute for Developmental Biology)

Abstract

Alzheimer's drugs for cancer? Notch genes encode a range of membrane receptors that regulate cell-fate decisions by influencing communication between adjacent cells. Two groups now report the involvement of Notch signals in controlling the fate of intestinal epithelial tissue. In addition, blockade of the Notch pathway with the γ-secretase inhibitor DBZ halted growth of adenomas (polyps) in the small intestine and colon. Various γ-secretase inhibitors are being developed for the treatment of Alzheimer's disease; this new work suggests that they might also be used to treat colorectal cancers.

Suggested Citation

  • Johan H. van Es & Marielle E. van Gijn & Orbicia Riccio & Maaike van den Born & Marc Vooijs & Harry Begthel & Miranda Cozijnsen & Sylvie Robine & Doug J. Winton & Freddy Radtke & Hans Clevers, 2005. "Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells," Nature, Nature, vol. 435(7044), pages 959-963, June.
    • Handle: RePEc:nat:nature:v:435:y:2005:i:7044:d:10.1038_nature03659
    DOI: 10.1038/nature03659
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    Cited by:

    1. Yi Liu & Efren Reyes & David Castillo-Azofeifa & Ophir D. Klein & Todd Nystul & Diane L. Barber, 2023. "Intracellular pH dynamics regulates intestinal stem cell lineage specification," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Jong Hoon Won & Jacob S. Choi & Joon-Il Jun, 2022. "CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Sophie K Kay & Heather A Harrington & Sarah Shepherd & Keith Brennan & Trevor Dale & James M Osborne & David J Gavaghan & Helen M Byrne, 2017. "The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt," PLOS Computational Biology, Public Library of Science, vol. 13(2), pages 1-28, February.
    4. Arafath K. Najumudeen & Sigrid K. Fey & Laura M. Millett & Catriona A. Ford & Kathryn Gilroy & Nuray Gunduz & Rachel A. Ridgway & Eve Anderson & Douglas Strathdee & William Clark & Colin Nixon & Jenni, 2024. "KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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