Normal epithelial cells create contiguous cell sheets that cover the surfaces of organs or the body surface, and that exhibit a distinctive apical and basal surface. Loss of this polarity contributes to epithelial-to-mesenchymal transition (EMT) and is associated with invasive phenotypes of cancer. Mutations to genes that regulate the polarized distribution of cellular proteins are known to contribute to cancer progression, but how polarity and tumorigenesis are linked is not known. Reischauer et al. found that a gene that regulates the polarity of epithelial cells in zebrafish, lethal giant larvae 2 (lgl2), suppresses EMT and malignant growth. ErbB2 signaling, which is disrupted in some forms of human cancer, is necessary for the genesis of neoplasia in zebrafish that lack the lgl2 gene. Thus, lgl2 is a tumor suppressor gene in vertebrates and Lgl2 mutant zebrafish should provide a valuable new cancer model.
Reischauer S, Levesque MP, Nüsslein-Volhard C, Sonawane M (2009). Lgl2 executes its function as a tumor suppressor by regulating ErbB signaling in the zebrafish epidermis. PLoS Genet. 5, e1000720.
