¹Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via Campi 287, I-41100 Modena, Italy

Correspondence: GP Rossini, E-mail: rossini.gianpaolo@unimore.it

Received 25 July 2003; Revised 15 October 2003; Accepted 13 December 2003.

Abstract

Yessotoxins (YTXs) are algal toxins that can be accumulated in edible molluscs. YTX treatment of MCF-7 breast cancer cells causes the accumulation of a 100 kDa fragment of E-cadherin, which we have named ECRA₁₀₀. A relative decrease in the concentrations of intact E-cadherin did not accompany the accumulation of ECRA₁₀₀ in cytosoluble extracts of MCF-7 cells on the first day of YTX treatment, but a collapse of the E-cadherin system was detected after 2–5 days of treatment with the toxin. An analysis of the general structure of ECRA₁₀₀ revealed that it consists of an E-cadherin fragment lacking the intracellular domain of the protein. ECRA₁₀₀ was not released into culture media of YTX-treated cells. Accumulation of ECRA₁₀₀ was observed in other epithelial cells, such as human intestine Caco-2 and MDCK cells after treatment with YTX. In turn, YTX could not induce accumulation of fragments of other members of the cadherin family, such as N-cadherin in the PC12 cell line and K-cadherin in sensitive cells (MCF-7, Caco-2, MDCK). The accumulation of a 100 kDa fragment of E-cadherin devoid of its intracellular domain induced by YTX was accompanied by reduced levels of - and -catenins bound to E-cadherin, without a concomitant decrease in the total cytosoluble pools of - and -catenins. Taken together, the results we obtained show that YTX causes the selective disruption of the E-cadherin–catenin system in epithelial cells, and raise some concern about the potential that an algal toxin found in seafood might disrupt the tumour suppressive functions of E-cadherin.