title: Cdc42 is involved in basal cell carcinoma carcinogenesis.
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.
authors.affiliation: U.O. Dermatologia, INRCA-IRCCS, Ancona, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Tucci
authors.forename: Guendalina
authors.initials: G
authors.lastname: Lucarini
authors.forename: Antonio
authors.initials: A
authors.lastname: Zizzi
authors.forename: Romina
authors.initials: R
authors.lastname: Rocchetti
authors.forename: Donatella
authors.initials: D
authors.lastname: Brancorsini
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Primio
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ricotti
mesh_terms: D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism*; D063646:Carcinogenesis / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000473:pathology*; D002448:Cell Adhesion; D016764:Cell Polarity; D006801:Humans; D009924:Organ Culture Techniques; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000473:pathology*; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015820:Cadherins; D020764:cdc42 GTP-Binding Protein