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Epigenetic disruption of cadherin-11 in human cancer metastasis

F Javier Carmona1, Alberto Villanueva, August Vidal

  • 1Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.

The Journal of Pathology
|March 1, 2012
PubMed

Insights

Epigenetic changes, like cadherin-11 (CDH11) promoter hypermethylation, are specific to cancer metastases. This silencing of CDH11 inhibits tumor growth and spread, offering insights into cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The molecular mechanisms driving cancer metastasis remain largely unknown.
  • Epigenetic alterations are dynamic and may influence cancer cell behavior during disease progression.

Purpose of the Study:

  • To investigate metastasis-specific epigenetic changes in human tumors.
  • To identify molecular targets involved in the biology of disseminated cancer cells.

Main Methods:

  • Utilized a DNA methylation microarray to compare paired primary tumors and lymph node metastases.
  • Employed in vitro and in vivo models to assess the functional role of cadherin-11 (CDH11).
  • Analyzed CDH11 5'-CpG island hypermethylation in patient samples.

Main Results:

  • Identified cadherin-11 (CDH11) promoter CpG island hypermethylation in lymph node metastases but not primary tumors.
  • Demonstrated CDH11 DNA methylation-associated transcriptional silencing in melanoma and head and neck cancer metastases.
  • Showed that CDH11 inhibits tumor growth, motility, and dissemination in experimental models.
  • Found CDH11 hypermethylation significantly confined to disseminated cancer cells in patients.

Conclusions:

  • Epigenetic alterations, specifically CDH11 promoter hypermethylation, are associated with cancer metastasis.
  • CDH11 acts as a tumor suppressor, inhibiting growth and spread.
  • These findings reveal metastasis-specific epigenetic events crucial for disease progression.

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