Cdc42 is involved in basal cell carcinoma carcinogenesis

Maria Giovanna Tucci, Guendalina Lucarini, Antonio Zizzi, Romina Rocchetti, Donatella Brancorsini, Roberto Di Primio, Francesca Ricotti, Giuseppe Ricotti

Research output: Contribution to journalArticle

Abstract

Basal cell carcinoma (BCC) is the most common type of skin cancer in older persons and is a rapidly rising incidence. E-cadherin-mediated cell-cell adhesion activates Cdc42, a Rho GTPase essential for cell polarity in numerous settings. No study has yet addressed a biological significance of Cdc42 alterations in BCC pathogenesis. Our aim was to investigate E-cadherin-dependent cell-cell contacts and Cdc42 activity in BCC formation. We evaluated E-cadherin and Cdc42 expression by immunohistochemistry and Western blot analysis in samples of 15 normal skin (NS) and 30 BCC (10 superficial, 9 nodular and 11 infiltrative subtypes). Low E-cadherin and high Cdc42 immunohistochemical expression were found in BCC samples compared with NS. E-cadherin staining was significantly reduced in infiltrative BCC compared with superficial and nodular. A significantly greater Cdc42 expression was observed in BCC compared with NS; moreover, superficial BCC had a significantly lower Cdc42 expression in respect to the other subtypes. Western blot analysis confirmed the significantly decreased E-cadherin expression in infiltrative BCC as well as Cdc42 reduction in superficial BCC in respect to the other subtypes. In BCC the increased Cdc42 in association with reduced E-cadherin might contribute to the disruption of adhesion mechanisms and to the loss of cell polarity, thus explaining a mechanism by which cancer cells can escape from the control of adjacent normal keratinocytes. Our study also showed that Cdc42 and E-cadherin expression differed according to aggressive behaviour of BCC subtypes and suggested important functions of these molecules in regulating tumour demarcation and progression.

Original languageEnglish
Pages (from-to)835-840
Number of pages6
JournalArchives of Dermatological Research
Volume305
Issue number9
DOIs
Publication statusPublished - Nov 2013

Keywords

  • Basal cell carcinoma
  • Cdc42
  • Cell polarity
  • E-cadherin

ASJC Scopus subject areas

  • Dermatology

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  • Cite this

    Tucci, M. G., Lucarini, G., Zizzi, A., Rocchetti, R., Brancorsini, D., Primio, R. D., Ricotti, F., & Ricotti, G. (2013). Cdc42 is involved in basal cell carcinoma carcinogenesis. Archives of Dermatological Research, 305(9), 835-840. https://doi.org/10.1007/s00403-013-1351-8