NEDD4和NEDD4L的潜在作用及其作为高发病率成年男性癌症治疗靶点的效用(综述)

IF 1.4 Q4 ONCOLOGY Molecular and clinical oncology Pub Date : 2023-09-01 DOI:10.3892/mco.2023.2664
Amjad Z Alrosan, Khaled Alrosan, Ghaith B Heilat, Rawan Alsharedeh, Rawan Abudalo, Muna Oqal, Abdelrahim Alqudah, Yasmin A Elmaghrabi
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摘要

术语“癌症”是指超过100种随时间逐渐显现的疾病,其特征是不受控制的细胞分裂。尽管恶性生长几乎可以发生在任何人体组织中,但所有形式癌症的潜在机制是一致的。国际癌症研究机构的GLOBOCAN 2020年度报告提供了全球癌症发病率和死亡率的最新情况。该报告预测,不包括非黑色素瘤皮肤癌,到2023年将有1930万新的癌症病例和超过1000万的癌症相关死亡病例。肺癌、前列腺癌和结肠癌是男性中最常见和最致命的癌症。人们认识到蛋白质的翻译后修饰(PTMs)是几乎所有细胞生物学过程,以及癌症发展和转移到其他身体器官所必需的。因此,ptm对蛋白质的行为有相当大的影响。各种ptm可能通过影响肿瘤的标志、代谢和肿瘤微环境的调节而具有有害作用。PTMs和基因变化/突变在癌变和癌症发展中是必不可少的。一个关键的PTM机制是蛋白质泛素化。值得注意的是,蛋白质泛素化级联的限速阶段被假设为e3连接酶介导的泛素化。大量研究表明,神经前体细胞表达发育下调蛋白4 (NEDD4) E3连接酶是在细胞过程中起重要作用的E3泛素连接酶之一。它调节蛋白质降解和底物泛素化。此外,研究表明NEDD4在各种恶性肿瘤中主要作为癌基因发挥作用,但在某些类型的肿瘤中也可以作为肿瘤抑制因子。本文就NEDD4作为一种抗癌蛋白在各种高发男性恶性肿瘤中的作用及NEDD4作为潜在肿瘤治疗靶点的意义进行综述。此外,本文还探讨了靶向NEDD4作为治疗人类恶性肿瘤的一种治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review).

The term 'cancer' refers to >100 disorders that progressively manifest over time and are characterized by uncontrolled cell division. Although malignant growth can occur in virtually any human tissue, the underlying mechanisms underlying all forms of cancer are consistent. The International Agency for Research on Cancer's annual GLOBOCAN 2020 report provided an update on the global cancer incidence and mortality. Excluding non-melanoma skin cancer, the report predicts that there will be 19.3 million new cancer cases and >10 million cancer-related fatalities in 2023. Lung, prostate, and colon cancers are the most prevalent and lethal cancers in males. It was recognized that post-translational modifications (PTMs) of proteins are necessary for almost all cellular biological processes, as well as in cancer development and metastasis to other bodily organs. Thus, PTMs have a considerable impact on how proteins behave. Various PTMs may have harmful roles by affecting the hallmarks of cancer, metabolism and the regulation of the tumor microenvironment. PTMs and genetic changes/mutations are essential in carcinogenesis and cancer development. A pivotal PTM mechanism is protein ubiquitination. Of note, the rate-limiting stage of the protein ubiquitination cascade is hypothesized to be E3-ligase-mediated ubiquitination. Numerous studies revealed that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) E3 ligase is among the E3 ubiquitin ligases that have essential roles in cellular processes. It regulates protein degradation and substrate ubiquitination. In addition, it has been shown that NEDD4 primarily functions as an oncogene in various malignancies but can also act as a tumor suppressor in certain types of tumor. In the present review, the roles of NEDD4 as an anticancer protein in various high-incidence male malignancies and the significance of NEDD4 as a potential cancer therapeutic target are discussed. In addition, the targeting of NEDD4 as a therapeutic strategy for the treatment of human malignancies is explored.

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