Epigenetic disruption of cadherin-11 in human cancer metastasis

F. Javier Carmona, Alberto Villanueva, August Vidal, Clara Muñoz, Sara Puertas, Rosa M. Penin, Montserrat Gomà, Amaia Lujambio, Josep M. Piulats, Ricard Mesía, Montse Sánchez-Céspedes, Manel Manós, Enric Condom, Suzanne A. Eccles, Manel Esteller

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Little is known about the molecular events occurring in the metastases of human tumours. Epigenetic alterations are dynamic lesions that change over the natural course of the disease, and so they might play a role in the biology of cancer cells that have departed from the primary tumour. Herein, we have adopted an epigenomic approach to identify some of these changes. Using a DNA methylation microarray platform to compare paired primary tumour and lymph node metastatic cell lines from the same patient, we observed cadherin-11 promoter CpG island hypermethylation as a likely target of the process. We found that CDH11 DNA methylation-associated transcriptional silencing occurred in the corresponding lymph node metastases of melanoma and head and neck cancer cells but not in the primary tumours. Using in vitro and in vivo cellular and mouse models for depleted or enhanced CDH11 activity, we also demonstrated that CDH11 acts as an inhibitor of tumour growth, motility and dissemination. Most importantly, the study of CDH11 5'-CpG island hypermethylation in primary tumours and lymph node metastases of cancer patients showed this epigenetic alteration to be significantly confined to the disseminated cells. Overall, these results indicate the existence of metastasis-specific epigenetic events that might contribute to the progression of the disease.

Original languageEnglish
Pages (from-to)230-240
Number of pages11
JournalJournal of Pathology
Volume228
Issue number2
DOIs
StatePublished - Oct 2012
Externally publishedYes

Keywords

  • DNA methylation
  • cadherin-11
  • epigenetics
  • metastasis

Fingerprint

Dive into the research topics of 'Epigenetic disruption of cadherin-11 in human cancer metastasis'. Together they form a unique fingerprint.

Cite this