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Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes

Author

Listed:
  • Patrick L. Leslie

    (University of North Carolina at Chapel Hill)

  • Yvonne L. Chao

    (University of North Carolina at Chapel Hill)

  • Yi-Hsuan Tsai

    (University of North Carolina at Chapel Hill)

  • Subrata K. Ghosh

    (University of North Carolina at Chapel Hill)

  • Alessandro Porrello

    (University of North Carolina at Chapel Hill)

  • Amanda E. D. Swearingen

    (University of North Carolina at Chapel Hill)

  • Emily B. Harrison

    (University of North Carolina at Chapel Hill)

  • Brian C. Cooley

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Joel S. Parker

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Lisa A. Carey

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Chad V. Pecot

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

Abstract

Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors.

Suggested Citation

  • Patrick L. Leslie & Yvonne L. Chao & Yi-Hsuan Tsai & Subrata K. Ghosh & Alessandro Porrello & Amanda E. D. Swearingen & Emily B. Harrison & Brian C. Cooley & Joel S. Parker & Lisa A. Carey & Chad V. P, 2019. "Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12222-5
    DOI: 10.1038/s41467-019-12222-5
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    Cited by:

    1. Steffen Mueller & Gail Dennison & Shujun Liu, 2021. "An Assessment on Ethanol-Blended Gasoline/Diesel Fuels on Cancer Risk and Mortality," IJERPH, MDPI, vol. 18(13), pages 1-23, June.

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