title: Biological influence of Hakai in cancer: a 10-year review.
abstract: In order to metastasize, cancer cells must first detach from the primary tumor, migrate, invade through tissues, and attach to a second site. Hakai was discovered as an E3 ubiquitin-ligase that mediates the posttranslational downregulation of E-cadherin, a major component of adherens junctions in epithelial cells that is characterized as a potent tumor suppressor and is modulated during various processes including epithelial-mesenchymal transition. Recent data have provided evidences for novel biological functional role of Hakai during tumor progression and other diseases. Here, we will review the knowledge that has been accumulated since Hakai discovery 10 years ago and its implication in human cancer disease. We will highlight the different signaling pathways leading to the influence on Hakai and suggest its potential usefulness as therapeutic target for cancer.
authors.affiliation: Servizo de Oncología Médica, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Aparicio
authors.forename: Manuel
authors.initials: M
authors.lastname: Valladares
authors.forename: Moisés
authors.initials: M
authors.lastname: Blanco
authors.forename: Guillermo
authors.initials: G
authors.lastname: Alonso
authors.forename: Angélica
authors.initials: A
authors.lastname: Figueroa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; C471638:CBLL1 protein, human; D044767:Ubiquitin-Protein Ligases