Hakin-1 is an inhibitor of the E3 ubiquitin ligase Hakai. It effectively blocks both overall ubiquitination mediated by Hakai and the specific ubiquitination of E-cadherin, thereby inhibiting the process of epithelial-mesenchymal transition (EMT). Hakin-1 can impede tumor progression and cancer metastasis and is utilized for research in colorectal cancer and other cancers.

Hakin-1 exhibits dose-dependent inhibition of cell viability in HT-29, LoVo, MDCK, HaKai-MDCK (clone-4), and HaKai-MDCK (clone-11) cells, with IC50 values of 289.2, 159.1, 265.6, 176.3, and 165.4 μM, respectively. Hakin-1 at concentrations of 50-100 μM enhances the expression of E-cadherin and Cortactin while reducing Vimentin levels, without altering mRNA levels in HT-29 cells. Over 21-28 days, Hakin-1 (50-100 μM) significantly diminishes tumor spheroid formation in HT-29 and HaKai-MDCK cells. Additionally, treatment with Hakin-1 (50-100 μM for 48 hours) results in decreased cell invasion and migration in HT-29, LoVo, and HaKai-MDCK cells.

Hakin-1 (5 mg/kg, intraperitoneal injection, 3 times a week, for 20 days) is effective in suppressing tumor growth in Hakai-MDCK tumor xenografts, which lack E-cadherin expression. This activity is associated with decreased expression of the mesenchymal marker N-cadherin and a reduction in pulmonary micrometastasis formation.