Novel therapeutic strategies against cancer metastasis: From Research to Innovation
Angélica Figueroa
Instituto de Investigación Biomédica A Coruña (INIBIC)
Carcinoma is the most common type of cancer, and arises from the malignant transformation of epithelial cells. At the early stages of carcinoma progression, a process known as epithelial-mesenchymal transition (EMT) takes place. EMT is characterized by the downregulation of E-cadherin, a tumor suppressor responsible for cell-cell adhesion in the epithelium. The E3 ubiquitin-ligase Hakai was the first reported posttranslational regulator of the E-cadherin stability, and its importance during tumor progression and disease has been widely demonstrated. E3 ubiquitin-ligase enzymes have recently emerged as promising therapeutic targets, as their specific inhibition would avoid wider side effects compared to other members of the ubiquitin pathway. We have identified a novel small-molecule inhibitor for Hakai, named Hakin-1, that mediated Hakai-dependent ubiquitination of E-cadherin. We have shown the antitumor action of Hakín-1 in vitro and in vivo. Therefore we proposed Hakai as a promising therapeutic agent for cancer treatment through the inhibition of EMT. On the other hand, we have also identified novel Hakai-interacting proteins implicated at early stages of tumor progression.