Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Leslie, PL; Chao, YL; Tsai, Y-H; Ghosh, SK; Porrello, A; Van Swearingen, AED; Harrison, EB; Cooley, BC; Parker, JS; Carey, LA; Pecot, CV

Published Date

  • September 13, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 4192 -

PubMed ID

  • 31519896

Pubmed Central ID

  • 31519896

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-12222-5

Language

  • eng