Open Access

MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3

  • Authors:
    • Mengting Ou
    • Xichao Xu
    • Ying Chen
    • Li Li
    • Lu Zhang
    • Yi Liao
    • Weichao Sun
    • Christine Quach
    • Jianguo Feng
    • Liling Tang
  • View Affiliations

  • Published online on: May 5, 2021     https://doi.org/10.3892/or.2021.8071
  • Article Number: 120
  • Copyright: © Ou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MDM2 proto‑oncogene, E3 ubiquitin protein ligase (MDM2) is a well‑known oncogene and has been reported to be closely associated with epithelial‑to‑mesenchymal transition (EMT). The present study first demonstrated that the expression levels of MDM2 were markedly increased in TGF‑β‑induced EMT using quantitative PCR and western blotting. In addition, MDM2 was demonstrated to be associated with pathological grade in clinical glioma samples by immunohistochemical staining. Furthermore, overexpression of MDM2 promoted EMT in glioma, lung cancer and breast cancer cell lines using a scratch wound migration assay. Subsequently, the present study explored the mechanism by which MDM2 promoted EMT and revealed that MDM2 induced EMT by upregulating EMT‑related transcription factors via activation of the B‑Raf signaling pathway through tyrosine 3‑monooxygenase activation protein ε using RNA sequencing and western blotting. This mechanism depended on the p53 gene. Furthermore, in vivo experiments and the colony formation experiment demonstrated that MDM2 could promote tumor progression and induce EMT via the B‑Raf signaling pathway. Since EMT contributes to increased drug resistance in tumor cells, the present study also explored the relationship between MDM2 and drug sensitivity using an MTT assay, and identified that MDM2 promoted cell insensitivity to silibinin treatment in an EMT‑dependent manner. This finding is crucial for the development of cancer therapies and can also provide novel research avenues for future biological and clinical studies.
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July-2021
Volume 46 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ou M, Xu X, Chen Y, Li L, Zhang L, Liao Y, Sun W, Quach C, Feng J, Tang L, Tang L, et al: MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3. Oncol Rep 46: 120, 2021
APA
Ou, M., Xu, X., Chen, Y., Li, L., Zhang, L., Liao, Y. ... Tang, L. (2021). MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3. Oncology Reports, 46, 120. https://doi.org/10.3892/or.2021.8071
MLA
Ou, M., Xu, X., Chen, Y., Li, L., Zhang, L., Liao, Y., Sun, W., Quach, C., Feng, J., Tang, L."MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3". Oncology Reports 46.1 (2021): 120.
Chicago
Ou, M., Xu, X., Chen, Y., Li, L., Zhang, L., Liao, Y., Sun, W., Quach, C., Feng, J., Tang, L."MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3". Oncology Reports 46, no. 1 (2021): 120. https://doi.org/10.3892/or.2021.8071