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XB-ART-44918
PLoS One. January 1, 2012; 7 (2): e32318.

Targeted inactivation of Snail family EMT regulatory factors by a Co(III)-Ebox conjugate.



Abstract
Snail family proteins are core EMT (epithelial-mesenchymal transition) regulatory factors that play essential roles in both development and disease processes and have been associated with metastasis in carcinomas. Snail factors are required for the formation of neural crest stem cells in most vertebrate embryos, as well as for the migratory invasive behavior of these cells. Snail factors have recently been linked to the formation of cancer stem cells, and expression of Snail proteins may be associated with tumor recurrence and resistance to chemotherapy and radiotherapy. We report that Co(III)-Ebox is a potent inhibitor of Snail-mediated transcriptional repression in breast cancer cells and in the neural crest of Xenopus. We further show that the activity of Co(III)-Ebox can be modulated by temperature, increasing the utility of this conjugate as a Snail inhibitor in model organisms. We exploit this feature to further delineate the requirements for Snail function during neural crest development, showing that in addition to the roles that Snail factors play in neural crest precursor formation and neural crest EMT/migration, inhibition of Snail function after the onset of neural crest migration leads to a loss of neural crest derived melanocytes. Co(III)-Ebox-mediated inhibition therefore provides a powerful tool for analysing the function of these core EMT factors with unparalleled temporal resolution. Moreover, the potency of Co(III)-Ebox as a Snail inhibitor in breast cancer cells suggests its potential as a therapeutic inhibitor of tumor progression and metastasis.

PubMed ID: 22393397
PMC ID: PMC3290632
Article link: PLoS One.
Grant support: R01CA114058 NCI NIH HHS , R01CA114058 NCI NIH HHS , R01CA114058 NCI NIH HHS , R01CA114058 NCI NIH HHS , R01CA114058 NCI NIH HHS , R01CA114058 NCI NIH HHS , U54CA151880 NCI NIH HHS , U54CA151880 NCI NIH HHS , U54CA151880 NCI NIH HHS , U54CA151880 NCI NIH HHS , U54CA151880 NCI NIH HHS , U54CA151880 NCI NIH HHS , R01 CA114058 NCI NIH HHS , R01 CA114058 NCI NIH HHS , R01 CA114058 NCI NIH HHS , R01 CA114058 NCI NIH HHS , R01 CA114058 NCI NIH HHS , R01 CA114058 NCI NIH HHS

Genes referenced: cdh1 egr2 foxd3 snai1 snai2 sox10 tubb2b twist1
Antibodies referenced:
Morpholinos referenced:
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