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LY6D marks pre-existing resistant basosquamous tumor subpopulations

Author

Listed:
  • Daniel Haensel

    (Stanford University School of Medicine)

  • Sadhana Gaddam

    (Stanford University School of Medicine)

  • Nancy Y. Li

    (Stanford University School of Medicine)

  • Fernanda Gonzalez

    (Stanford University School of Medicine)

  • Tiffany Patel

    (Stanford University School of Medicine)

  • Jeffrey M. Cloutier

    (Stanford University School of Medicine)

  • Kavita Y. Sarin

    (Stanford University School of Medicine)

  • Jean Y. Tang

    (Stanford University School of Medicine)

  • Kerri E. Rieger

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Sumaira Z. Aasi

    (Stanford University School of Medicine)

  • Anthony E. Oro

    (Stanford University School of Medicine)

Abstract

Improved response to canonical therapies requires a mechanistic understanding of dynamic tumor heterogeneity by identifying discrete cellular populations with enhanced cellular plasticity. We have previously demonstrated distinct resistance mechanisms in skin basal cell carcinomas, but a comprehensive understanding of the cellular states and markers associated with these populations remains poorly understood. Here we identify a pre-existing resistant cellular population in naive basal cell carcinoma tumors marked by the surface marker LY6D. LY6D+ tumor cells are spatially localized and possess basal cell carcinoma and squamous cell carcinoma-like features. Using computational tools, organoids, and spatial tools, we show that LY6D+ basosquamous cells represent a persister population lying on a central node along the skin lineage-associated spectrum of epithelial states with local environmental and applied therapies determining the kinetics of accumulation. Surprisingly, LY6D+ basosquamous populations exist in many epithelial tumors, such as pancreatic adenocarcinomas, which have poor outcomes. Overall, our results identify the resistant LY6D+ basosquamous population as an important clinical target and suggest strategies for future therapeutic approaches to target them.

Suggested Citation

  • Daniel Haensel & Sadhana Gaddam & Nancy Y. Li & Fernanda Gonzalez & Tiffany Patel & Jeffrey M. Cloutier & Kavita Y. Sarin & Jean Y. Tang & Kerri E. Rieger & Sumaira Z. Aasi & Anthony E. Oro, 2022. "LY6D marks pre-existing resistant basosquamous tumor subpopulations," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35020-y
    DOI: 10.1038/s41467-022-35020-y
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    References listed on IDEAS

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    1. Catherine D. Yao & Daniel Haensel & Sadhana Gaddam & Tiffany Patel & Scott X. Atwood & Kavita Y. Sarin & Ramon J. Whitson & Siegen McKellar & Gautam Shankar & Sumaira Aasi & Kerri Rieger & Anthony E. , 2020. "AP-1 and TGFß cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Shuxiong Wang & Michael L. Drummond & Christian F. Guerrero-Juarez & Eric Tarapore & Adam L. MacLean & Adam R. Stabell & Stephanie C. Wu & Guadalupe Gutierrez & Bao T. That & Claudia A. Benavente & Qi, 2020. "Single cell transcriptomics of human epidermis identifies basal stem cell transition states," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    3. Adriana Sánchez-Danés & Jean-Christophe Larsimont & Mélanie Liagre & Eva Muñoz-Couselo & Gaëlle Lapouge & Audrey Brisebarre & Christine Dubois & Mariano Suppa & Vijayakumar Sukumaran & Véronique del M, 2018. "A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy," Nature, Nature, vol. 562(7727), pages 434-438, October.
    4. Brian Biehs & Gerrit J. P. Dijkgraaf & Robert Piskol & Bruno Alicke & Soufiane Boumahdi & Franklin Peale & Stephen E. Gould & Frederic J. Sauvage, 2018. "A cell identity switch allows residual BCC to survive Hedgehog pathway inhibition," Nature, Nature, vol. 562(7727), pages 429-433, October.
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    Cited by:

    1. Nancy Yanzhe Li & Weiruo Zhang & Daniel Haensel & Anna R. Jussila & Cory Pan & Sadhana Gaddam & Sylvia K. Plevritis & Anthony E. Oro, 2024. "Basal-to-inflammatory transition and tumor resistance via crosstalk with a pro-inflammatory stromal niche," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Daniel Haensel & Bence Daniel & Sadhana Gaddam & Cory Pan & Tania Fabo & Jeremy Bjelajac & Anna R. Jussila & Fernanda Gonzalez & Nancy Yanzhe Li & Yun Chen & JinChao Hou & Tiffany Patel & Sumaira Aasi, 2023. "Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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