ID1 overexpression promotes HCC progression by amplifying the AURKA/Myc signaling pathway

  • Authors:
    • Man Wu
    • Yuhong Zhou
    • Chengming Fei
    • Tianyi Chen
    • Xin Yin
    • Lan Zhang
    • Zhenggang Ren
  • View Affiliations

  • Published online on: July 1, 2020     https://doi.org/10.3892/ijo.2020.5092
  • Pages: 845-857
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Abstract

Hepatocellular carcinoma (HCC) is the fourth most common cancer type worldwide, with a poor prognosis and high mortality rate. The aim of the present study was to investigate the mechanisms underlying HCC progression to potentially benefit the development of effective therapies for advanced HCC. The present study reported a novel mechanism that promotes the HCC malignant phenotype, in which the inhibitor of differentiation 1 (ID1) activates the aurora kinase A (AURKA)/Myc signaling pathway. Specifically, a high expression of ID1 promoted a highly malignant phenotype of HCC cells that exhibit enhanced metastatic ability and drug resistance. However, the effects of ID1 were markedly reversed by the AURKA inhibitor VX689 and the Myc inhibitor 10058‑F4. Further studies demonstrated that ID1 competitively binds with anaphase‑promoting complex/cyclosome Cdh1 (APC/CCdh1), which is responsible for ubiquitination‑mediated AURKA protein degradation, resulting in upregulation of AURKA. Increased AURKA expression subsequently enhanced Myc expression at both transcriptional and post‑transcriptional level, leading to amplification of the Myc oncogenic signaling pathway. This novel ID1/AURKA/Myc axis could be a promising therapeutic target for the development of effective therapeutic strategies for advanced HCC.
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September-2020
Volume 57 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Wu M, Zhou Y, Fei C, Chen T, Yin X, Zhang L and Ren Z: ID1 overexpression promotes HCC progression by amplifying the AURKA/Myc signaling pathway. Int J Oncol 57: 845-857, 2020
APA
Wu, M., Zhou, Y., Fei, C., Chen, T., Yin, X., Zhang, L., & Ren, Z. (2020). ID1 overexpression promotes HCC progression by amplifying the AURKA/Myc signaling pathway. International Journal of Oncology, 57, 845-857. https://doi.org/10.3892/ijo.2020.5092
MLA
Wu, M., Zhou, Y., Fei, C., Chen, T., Yin, X., Zhang, L., Ren, Z."ID1 overexpression promotes HCC progression by amplifying the AURKA/Myc signaling pathway". International Journal of Oncology 57.3 (2020): 845-857.
Chicago
Wu, M., Zhou, Y., Fei, C., Chen, T., Yin, X., Zhang, L., Ren, Z."ID1 overexpression promotes HCC progression by amplifying the AURKA/Myc signaling pathway". International Journal of Oncology 57, no. 3 (2020): 845-857. https://doi.org/10.3892/ijo.2020.5092