Selective disruption of the E-cadherin-catenin system by an algal toxin.
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 ECRA(100). A relative decrease in the concentrations of intact E-cadherin did not accompany the accumulation of ECRA(100) 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 ECRA(100) revealed that it consists of an E-cadherin fragment lacking the intracellular domain of the protein. ECRA(100) was not released into culture media of YTX-treated cells. Accumulation of ECRA(100) 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 beta- and gamma-catenins bound to E-cadherin, without a concomitant decrease in the total cytosoluble pools of beta- and gamma-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.
Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via Campi 287, I-41100 Modena, Italy.
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Ronzitti
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Callegari
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Malaguti
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Rossini
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018938:Caco-2 Cells / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D008978:Mollusk Venoms / Q000494:pharmacology*; D035964:Oxocins / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects; D011233:Precipitin Tests; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004988:Ethers, Cyclic; D008978:Mollusk Venoms; D035964:Oxocins; D015534:Trans-Activators; D051176:beta Catenin; C066632:yessotoxin; C087310:K cadherin