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Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis

Author

Listed:
  • Zongzhao Zhai

    (Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Shu Kondo

    (Invertebrate Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics)

  • Nati Ha

    (Biochemistry Center, University of Heidelberg)

  • Jean-Philippe Boquete

    (Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Michael Brunner

    (Biochemistry Center, University of Heidelberg)

  • Ryu Ueda

    (Invertebrate Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics)

  • Bruno Lemaitre

    (Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL))

Abstract

Stem cell self-renewal and differentiation are coordinated to maintain tissue homeostasis and prevent cancer. Mutations causing stem cell proliferation are traditionally the focus of cancer studies. However, the contribution of the differentiating stem cell progenies in tumorigenesis is poorly characterized. Here we report that loss of the SOX transcription factor, Sox21a, blocks the differentiation programme of enteroblast (EB), the intestinal stem cell progeny in the adult Drosophila midgut. This results in EB accumulation and formation of tumours. Sox21a tumour initiation and growth involve stem cell proliferation induced by the unpaired 2 mitogen released from accumulating EBs generating a feed-forward loop. EBs found in the tumours are heterogeneous and grow towards the intestinal lumen. Sox21a tumours modulate their environment by secreting matrix metalloproteinase and reactive oxygen species. Enterocytes surrounding the tumours are eliminated through delamination allowing tumour progression, a process requiring JNK activation. Our data highlight the tumorigenic properties of transit differentiating cells.

Suggested Citation

  • Zongzhao Zhai & Shu Kondo & Nati Ha & Jean-Philippe Boquete & Michael Brunner & Ryu Ueda & Bruno Lemaitre, 2015. "Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10219
    DOI: 10.1038/ncomms10219
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    Cited by:

    1. Xingting Guo & Chenhui Wang & Yongchao Zhang & Ruxue Wei & Rongwen Xi, 2024. "Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Kathyani Parasram & Amy Zuccato & Minjeong Shin & Reegan Willms & Brian DeVeale & Edan Foley & Phillip Karpowicz, 2024. "The emergence of circadian timekeeping in the intestine," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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