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SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma

Author

Listed:
  • Jasmin M. Siegle

    (The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center)

  • Alice Basin

    (The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center)

  • Ana Sastre-Perona

    (The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center)

  • Yoshiya Yonekubo

    (The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center)

  • Jessie Brown

    (The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center)

  • Rachel Sennett

    (Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai)

  • Michael Rendl

    (Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai)

  • Aristotelis Tsirigos

    (Center for Health Informatics and Bioinformatics, New York University Langone Medical Center)

  • John A. Carucci

    (The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center)

  • Markus Schober

    (The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center)

Abstract

Although the principles that balance stem cell self-renewal and differentiation in normal tissue homeostasis are beginning to emerge, it is still unclear whether cancer cells with tumour initiating potential are similarly governed, or whether they have acquired distinct mechanisms to sustain self-renewal and long-term tumour growth. Here we show that the transcription factor Sox2, which is not expressed in normal skin epithelium and is dispensable for epidermal homeostasis, marks tumour initiating cells (TICs) in cutaneous squamous cell carcinomas (SCCs). We demonstrate that Sox2 is required for SCC growth in mouse and human, where it enhances Nrp1/Vegf signalling to promote the expansion of TICs along the tumour–stroma interface. Our findings suggest that distinct transcriptional programmes govern self-renewal and long-term growth of TICs and normal skin epithelial stem and progenitor cells. These programmes present promising diagnostic markers and targets for cancer-specific therapies.

Suggested Citation

  • Jasmin M. Siegle & Alice Basin & Ana Sastre-Perona & Yoshiya Yonekubo & Jessie Brown & Rachel Sennett & Michael Rendl & Aristotelis Tsirigos & John A. Carucci & Markus Schober, 2014. "SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5511
    DOI: 10.1038/ncomms5511
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    Cited by:

    1. Mingsen Li & Huaxing Huang & Bofeng Wang & Shaoshuai Jiang & Huizhen Guo & Liqiong Zhu & Siqi Wu & Jiafeng Liu & Li Wang & Xihong Lan & Wang Zhang & Jin Zhu & Fuxi Li & Jieying Tan & Zhen Mao & Chunqi, 2022. "Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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