Alrosan Amjad Z, Heilat Ghaith B, Alrosan Khaled, Shannag Ahmad, Alshalout Ehab M
Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, 13133, Jordan.
Department of General Surgery and Urology, Faculty of Medicine, The Jordan University of Science and Technology, Irbid, 22110, Jordan.
Med Oncol. 2025 May 6;42(6):200. doi: 10.1007/s12032-025-02751-z.
Currently, breast cancer (BC) and ovarian cancer (OC) are the most prevalent forms of cancer among women worldwide. Even though BC has a favorable outlook when detected early and managed appropriately compared to OC, the spread of BC and OC to other parts of the body, known as metastasis, is a significant cause of death. A robust association exists between genetic and protein alterations and post-translational modifications (PTMs), significantly impacting tumor formation, advancement, and prognosis. Ubiquitination, a crucial PTM, regulates almost all aspects of cellular function, and E3-ligase-mediated ubiquitination is a pivotal process that controls the speed of the protein ubiquitination cascade. NEDD4-1, a neural developmentally downregulated protein 4-1, is a crucial E3 ligase that plays a significant role in regulating several proteins that have important functions in the development and progression of BC and OC, thus controlling BC and OC cells' movement, infiltration, and multiplication. This review discusses the latest developments in comprehending NEDD4-1 substrates and their involvement in signal transduction pathways in BC and OC. NEDD4-1 likely serves as a novel diagnostic indicator and a target for therapy in the battle against both cancers.
目前，乳腺癌（BC）和卵巢癌（OC）是全球女性中最常见的癌症形式。尽管与卵巢癌相比，乳腺癌若能早期发现并得到妥善治疗，预后较好，但乳腺癌和卵巢癌扩散至身体其他部位（即转移）是导致死亡的重要原因。基因和蛋白质改变与翻译后修饰（PTM）之间存在紧密联系，对肿瘤的形成、发展和预后有重大影响。泛素化是一种关键的翻译后修饰，几乎调节细胞功能的各个方面，而E3连接酶介导的泛素化是控制蛋白质泛素化级联反应速度的关键过程。NEDD4-1（一种在神经发育过程中表达下调的蛋白质4-1）是一种关键的E3连接酶，在调节多种对乳腺癌和卵巢癌的发生发展具有重要作用的蛋白质方面发挥着重要作用，从而控制乳腺癌和卵巢癌细胞的移动、浸润和增殖。本综述讨论了在理解NEDD4-1底物及其在乳腺癌和卵巢癌信号转导途径中的作用方面的最新进展。NEDD4-1可能是对抗这两种癌症的新型诊断指标和治疗靶点。
