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Cdc42 is involved in basal cell carcinoma carcinogenesis

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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.

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. U.O. Dermatologia, INRCA-IRCCS, Ancona, Italy

    Maria Giovanna Tucci, Francesca Ricotti & Giuseppe Ricotti

  2. Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Via Tronto 10/A, 60020, Ancona, Torrette, Italy

    Guendalina Lucarini & Roberto Di Primio

  3. Dipartimento di Neuroscienze, Sezione di Anatomia Patologica, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Lancisi-Salesi-Umberto I, Ancona, Torrette, Italy

    Antonio Zizzi, Romina Rocchetti & Donatella Brancorsini

Authors
  1. Maria Giovanna Tucci
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  2. Guendalina Lucarini
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  3. Antonio Zizzi
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  4. Romina Rocchetti
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  5. Donatella Brancorsini
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  6. Roberto Di Primio
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  7. Francesca Ricotti
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  8. Giuseppe Ricotti
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Corresponding author

Correspondence to Guendalina Lucarini.

Additional information

M. G. Tucci and G. Lucarini equally contributed to this work.

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Tucci, M.G., Lucarini, G., Zizzi, A. et al. Cdc42 is involved in basal cell carcinoma carcinogenesis. Arch Dermatol Res 305, 835–840 (2013). https://doi.org/10.1007/s00403-013-1351-8

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  • DOI: https://doi.org/10.1007/s00403-013-1351-8

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