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

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.

• Authors: Patrick L Leslie, Yvonne L Chao, Yi-Hsuan Tsai, Subrata K Ghosh, Alessandro Porrello, Amanda E D Van Swearingen, Emily B Harrison, Brian C Cooley, Joel S Parker, Lisa A Carey, Chad V Pecot
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 4192 (09 13 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31519896 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hdac11 protein, mouse
• Histone Deacetylases

Topics

• Animals
• Blotting, Western
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (genetics, physiology)
• Chromatin Immunoprecipitation
• DNA Methylation (genetics, physiology)
• Flow Cytometry
• HEK293 Cells
• Histone Deacetylases (genetics, metabolism)
• Humans
• Lymph Nodes (metabolism, pathology)
• Lymphatic Metastasis (pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Real-Time Polymerase Chain Reaction