Open Access

HECTD1 regulates the expression of SNAIL: Implications for epithelial‑mesenchymal transition

  • Authors:
    • Xinggang Wang
    • Christian De Geyter
    • Zanhui Jia
    • Ya Peng
    • Hong Zhang
  • View Affiliations

  • Published online on: February 27, 2020     https://doi.org/10.3892/ijo.2020.5002
  • Pages: 1186-1198
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As a transcription factor, SNAIL plays a crucial role in embryonic development and cancer progression by mediating epithelial‑mesenchymal transition (EMT); however, post‑translational modifications, such as ubiquitination, which control the degradation of SNAIL have been observed to affect its functional role in EMT. In a previous study by the authors, it was demonstrated that the HECT domain E3 ubiquitin ligase 1 (HECTD1) regulated the dynamic nature of adhesive structures. In the present study, HECTD1 was observed to interact with SNAIL and regulate its stability through ubiquitination, and the knockdown of HECTD1 increased the expression levels of SNAIL. HECTD1 was discovered to contain putative nuclear localization and export signals that facilitated its translocation between the cytoplasm and nucleus, a process regulated by epidermal growth factor (EGF). Treatment with leptomycin B resulted in the nuclear retention of HECTD1, which was associated with the loss of SNAIL expression. The knockdown of HECTD1 in HeLa cells increased cell migration and induced a mesenchymal phenotype, in addition to demonstrating sustained EGF signaling, which was observed through increased phosphorylated ERK expression levels. Under hypoxic conditions, HECTD1 expression levels were decreased by microRNA (miRNA or miR)‑210. Upon the observation of genetic abnormalities in the HECTD1 gene in cervical cancer specimens, it was observed that the decreased expression levels of HECTD1 were significantly associated with a poor patient survival. Thus, it was hypothesized that HECTD1 may regulate EMT through the hypoxia/hypoxia inducible factor 1α/miR‑210/HECTD1/SNAIL signaling pathway and the EGF/EGF receptor/HECTD1/ERK/SNAIL signaling pathway in cervical cancer. On the whole, the data of the present study indicated that HECTD1 serves as an E3 ubiquitin ligase to mediate the stability of SNAIL proteins.

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May 2020
Volume 56 Issue 5

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

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APA
Wang, X., De Geyter, C., Jia, Z., Peng, Y., & Zhang, H. (2020). HECTD1 regulates the expression of SNAIL: Implications for epithelial‑mesenchymal transition. International Journal of Oncology, 56, 1186-1198. https://doi.org/10.3892/ijo.2020.5002
MLA
Wang, X., De Geyter, C., Jia, Z., Peng, Y., Zhang, H."HECTD1 regulates the expression of SNAIL: Implications for epithelial‑mesenchymal transition". International Journal of Oncology 56.5 (2020): 1186-1198.
Chicago
Wang, X., De Geyter, C., Jia, Z., Peng, Y., Zhang, H."HECTD1 regulates the expression of SNAIL: Implications for epithelial‑mesenchymal transition". International Journal of Oncology 56, no. 5 (2020): 1186-1198. https://doi.org/10.3892/ijo.2020.5002