Servizo de Oncología Médica, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
Cancer Metastasis Rev. 2012 Jun;31(1-2):375-86. doi: 10.1007/s10555-012-9348-x.
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.
为了转移，癌细胞必须首先从原发性肿瘤上脱离，迁移，穿过组织侵入，并附着在第二个部位。Hakai 被发现是一种 E3 泛素连接酶，它介导 E-钙黏蛋白的翻译后下调，E-钙黏蛋白是上皮细胞黏附连接的主要成分，具有强大的肿瘤抑制作用，并在包括上皮-间充质转化在内的各种过程中进行调节。最近的数据为 Hakai 在肿瘤进展和其他疾病中的新生物学功能作用提供了证据。在这里，我们将回顾自 Hakai 发现 10 年来积累的知识及其在人类癌症疾病中的意义。我们将强调导致 Hakai 影响的不同信号通路，并提出将其作为癌症治疗靶点的潜在用途。
