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

  • Authors:
    • Amjad Z. Alrosan
    • Khaled Alrosan
    • Ghaith B. Heilat
    • Rawan Alsharedeh
    • Rawan Abudalo
    • Muna Oqal
    • Abdelrahim Alqudah
    • Yasmin A. Elmaghrabi
  • View Affiliations / Copyright

    Affiliations: 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, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The Yarmouk University, Irbid 21163, Jordan, Department of Pharmaceutical Technology, Faculty of Pharmacy, The Hashemite University, Zarqa 13133, Jordan, Wizard Pharmacy Willetton, Perth 6155, Western Australia
    Copyright: © Alrosan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 68
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    Published online on: July 18, 2023
       https://doi.org/10.3892/mco.2023.2664
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Abstract

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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Copy and paste a formatted citation
Spandidos Publications style
Alrosan AZ, Alrosan K, Heilat GB, Alsharedeh R, Abudalo R, Oqal M, Alqudah A and Elmaghrabi YA: Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review). Mol Clin Oncol 19: 68, 2023.
APA
Alrosan, A.Z., Alrosan, K., Heilat, G.B., Alsharedeh, R., Abudalo, R., Oqal, M. ... Elmaghrabi, Y.A. (2023). Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review). Molecular and Clinical Oncology, 19, 68. https://doi.org/10.3892/mco.2023.2664
MLA
Alrosan, A. Z., Alrosan, K., Heilat, G. B., Alsharedeh, R., Abudalo, R., Oqal, M., Alqudah, A., Elmaghrabi, Y. A."Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review)". Molecular and Clinical Oncology 19.3 (2023): 68.
Chicago
Alrosan, A. Z., Alrosan, K., Heilat, G. B., Alsharedeh, R., Abudalo, R., Oqal, M., Alqudah, A., Elmaghrabi, Y. A."Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review)". Molecular and Clinical Oncology 19, no. 3 (2023): 68. https://doi.org/10.3892/mco.2023.2664
Copy and paste a formatted citation
x
Spandidos Publications style
Alrosan AZ, Alrosan K, Heilat GB, Alsharedeh R, Abudalo R, Oqal M, Alqudah A and Elmaghrabi YA: Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review). Mol Clin Oncol 19: 68, 2023.
APA
Alrosan, A.Z., Alrosan, K., Heilat, G.B., Alsharedeh, R., Abudalo, R., Oqal, M. ... Elmaghrabi, Y.A. (2023). Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review). Molecular and Clinical Oncology, 19, 68. https://doi.org/10.3892/mco.2023.2664
MLA
Alrosan, A. Z., Alrosan, K., Heilat, G. B., Alsharedeh, R., Abudalo, R., Oqal, M., Alqudah, A., Elmaghrabi, Y. A."Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review)". Molecular and Clinical Oncology 19.3 (2023): 68.
Chicago
Alrosan, A. Z., Alrosan, K., Heilat, G. B., Alsharedeh, R., Abudalo, R., Oqal, M., Alqudah, A., Elmaghrabi, Y. A."Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review)". Molecular and Clinical Oncology 19, no. 3 (2023): 68. https://doi.org/10.3892/mco.2023.2664
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