Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes.
Patrick L LeslieYvonne L ChaoYi-Hsuan TsaiSubrata K GhoshAlessandro PorrelloAmanda E D Van SwearingenEmily B HarrisonBrian C CooleyJoel S ParkerLisa A CareyChad V PecotPublished in: Nature communications (2019)
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.
Keyphrases
- histone deacetylase
- lymph node
- genome wide
- neoadjuvant chemotherapy
- sentinel lymph node
- childhood cancer
- poor prognosis
- papillary thyroid
- gene expression
- risk assessment
- transcription factor
- dna methylation
- early stage
- squamous cell
- young adults
- internal carotid artery
- radiation therapy
- long non coding rna
- free survival