Hakin-1 (Hakai inhibitor-1) is a specific small molecule inhibitor of the E3 ubiquitin-ligase Hakai, reduces Hakai-mediated total ubiquitination and Hakai-mediated ubiquitination of E-cadherin.
Hakin-1 strongly reduces the ubiquitination mediated by Hakai in a dose-dependent manner, does not affect ubiquitination when Hakai was not overexpressed.
Hakin-1 inhibits Hakai-mediated ubiquitination without affecting Hakai protein levels.
Hakin-1 induces cytotoxicity and an epithelial phenotype on epithelial tumour cell lines HT-29 and LoVo cells.
Hakin-1 increases the amount of E-cadherin levels at cell-cell contacts in HT-29 and LoVo cells, induces epithelial differentiation.
Hakin-1 reduces cell invasion and cell migration, and inhibits proliferation of epithelial tumour cells.
Hakin-1 inhibits tumour growth in Hakai-MDCK xenografted mice apparently without systemic toxicity.
Hakin-1 reduces N-cadherin mesenchymal markers in tumour xenografts and lung micrometastasis in vivo.