Role of epithelial–mesenchymal transition involved molecules in the progression of cutaneous melanoma

Daniela Murtas, Cristina Maxia, Andrea Diana, Luca Pilloni, Claudia Corda, Luigi Minerba, Sara Tomei, Franca Piras, Caterina Ferreli, Maria Teresa Perra

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Epithelial–mesenchymal transition (EMT) has been suggested to have a driving role in the acquisition of a metastatic potential by melanoma cells. Important hallmarks of EMT include both E-cadherin downregulation and increased expression of N-cadherin. This switch in distinct classes of adhesion molecules leads melanoma cells to lose contact with adjacent keratinocytes and interact instead with stromal fibroblasts and endothelial cells, thus promoting dermal and vascular melanoma invasion. Consequently, tumor cells migrate to distant host tissues and establish metastases. A key regulator in the induction of EMT in melanoma is the Notch1 signaling pathway that, when activated, is prompt to upregulate N-cadherin expression. By means of this strategy, melanoma cells gain enhanced survival, proliferation and invasion properties, driving the tumor toward a more aggressive phenotype. On the basis of these statements, the present study aimed to investigate the possible association between N-cadherin and Notch1 presence in primary cutaneous melanomas and lymph node metastases. Our results from immunohistochemical analysis confirmed a positive correlation between N-cadherin and Notch1 presence in the same tumor samples. Moreover, this study highlighted that a concomitant high expression of N-cadherin and Notch1, both in primary lesions and in lymph node metastases, predicts an adverse clinical outcome in melanoma patients. Therefore, N-cadherin and Notch1 co-presence can be monitored as a predictive factor in early- and advanced-stage melanomas and open additional therapeutic targets for the restraint of melanoma metastasis.

Original languageEnglish
Pages (from-to)639-649
Number of pages11
JournalHistochemistry and Cell Biology
Volume148
Issue number6
DOIs
Publication statusPublished - 1 Dec 2017

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Keywords

  • Cutaneous melanoma
  • Immunohistochemistry
  • N-cadherin
  • Notch1
  • Survival

ASJC Scopus subject areas

  • Histology
  • Molecular Biology
  • Medical Laboratory Technology
  • Cell Biology

Cite this

Murtas, D., Maxia, C., Diana, A., Pilloni, L., Corda, C., Minerba, L., Tomei, S., Piras, F., Ferreli, C., & Perra, M. T. (2017). Role of epithelial–mesenchymal transition involved molecules in the progression of cutaneous melanoma. Histochemistry and Cell Biology, 148(6), 639-649. https://doi.org/10.1007/s00418-017-1606-0