Tumour Suppression: Ejector Seat

ReseaRch highlights

Nature Reviews Cancer | AoP, published online 14 october 2010; doi:10.1038/nrc2951

tumOuR SuPPRESSION Ejector seat Exosomes are small vesicles that are increased expression of the but not secreted by various cells under certain tetraspanin CD9 is associ- E-cadherin, conditions. They have recently gained ated with reduced Wnt suggesting prominence in cancer research owing signalling in tumour cells that E-cadherin to their capacity to carry mRNAs, and that the tetraspanin is required for β-catenin secretion microRNAs, and pro-oncogenic CD82 is a known in exosomes. and pro-angiogenic proteins and tumour suppressor. The molecular mechanisms deliver them to surrounding cells. They showed that responsible for CD82- and Tetraspanin transmembrane proteins increased expression CD9-mediated inclusion of an have been implicated in the forma- of CD9 or CD82, but E-cadherin–β-catenin complex into tion and secretion of exosomes, as not the tetraspanin exosomes need to be identified. well as in the suppression of tumour CD63, reduced the How tetraspanins promote exo- development. A paper published Wnt-mediated some formation also remains to be in the Journal of Cell Biology now activation of a elucidated. However, these findings implicates both tetraspanins and β-catenin–luciferase reporter clearly indicate that exosomes are an exosomes in the inhibition of the gene. Both CD9 and CD82 expres- alternative pathway for regulating Wnt–β-catenin pathway. sion reduced the protein levels of levels of β-catenin and canonical Wnt β-catenin is a crucial downstream β-catenin in cells, but this did not signalling and provide a biological regulator of the canonical Wnt occur through the proteasomal or explanation for the association of exosomes are pathway. Its levels in the nucleus lysosomal degradation of β-catenin. increased CD9 or CD82 expression an alternative are carefully controlled through Instead, expression of CD9 or CD82 with the reduced expression of Wnt phosphorylation, ubiquitylation and in HEK 293T cells promoted the target genes, and the correlation of pathway for proteasomal degradation. However, formation and secretion of exosomes reduced CD9 or CD82 expression regulating levels β-catenin also resides at the cell that contained β-catenin. Further with tumour progression. of β-catenin and membrane where it binds with experiments showed that E-cadherin, Nicola McCarthy canonical Wnt cadherins to form adherens junctions β-catenin and CD82 could be co- ORIGINAL RESEARCH PAPER Chairoungdua, A. signalling that are involved in cell adhesion. immunoprecipitated from cells, and et al. Exosome release of β-catenin: a novel Arthit Chairoungdua and colleagues that β-catenin secretion in exosomes mechanism that antagonizes Wnt signaling. J. Cell Biol. 190, 1079–1091 (2010) noted from the literature that was reduced in cells expressing CD82