Metastasis remains the leading causes of death in cancer patients. The epithelial to mesenchymal transition (EMT) is proposed to underlie the metastatic process, allowing cells to evade tumor primary site. Dissecting the pathways associated to EMT is essential to develop cancer therapeutic strategies. Using our model of mammary carcinogenesis, based on the rat cancer stem cell LA7 (LA7CSCs) that recapitulates the entire process of tumor development including metastasis formation, we identified miRNA-a* up-regulated during EMT occurring in vivo after the injection of a single LA7CSC. We demonstrated that ectopic expression of miRNA-a* in LA7CSCs results in CDH1 and CTNN-?1 modulation and recapitulates the fibroblast-like LA7 counterpart-phenotype (LA7E) and that TGF?-induced EMT results in miRNA-a* up-regulation through TWIST1 induction, while the down-regulation of miRNA-a* abrogates the invasion capacity of the LA7E both in 3D cultures and in vivo. Our results suggest the involvement of miRNA-a* in the commitment of LA7CSCs to the EMT program.
Contribution of miRNA-a* to epithelial-mesenchymal transition via E-cadherin/?-catenin complex destabilization
Valentina Martino;Valeria Tria;Paride Pelucchi;Ileana Zucchi;
2012
Abstract
Metastasis remains the leading causes of death in cancer patients. The epithelial to mesenchymal transition (EMT) is proposed to underlie the metastatic process, allowing cells to evade tumor primary site. Dissecting the pathways associated to EMT is essential to develop cancer therapeutic strategies. Using our model of mammary carcinogenesis, based on the rat cancer stem cell LA7 (LA7CSCs) that recapitulates the entire process of tumor development including metastasis formation, we identified miRNA-a* up-regulated during EMT occurring in vivo after the injection of a single LA7CSC. We demonstrated that ectopic expression of miRNA-a* in LA7CSCs results in CDH1 and CTNN-?1 modulation and recapitulates the fibroblast-like LA7 counterpart-phenotype (LA7E) and that TGF?-induced EMT results in miRNA-a* up-regulation through TWIST1 induction, while the down-regulation of miRNA-a* abrogates the invasion capacity of the LA7E both in 3D cultures and in vivo. Our results suggest the involvement of miRNA-a* in the commitment of LA7CSCs to the EMT program.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
