Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA

  • Authors:
    • Liwei Li
    • Yue Song
    • Qing Liu
    • Xi Liu
    • Rui Wang
    • Chunsheng Kang
    • Qingyu Zhang
  • View Affiliations

  • Published online on: March 7, 2018     https://doi.org/10.3892/ijmm.2018.3544
  • Pages: 3629-3641
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Abstract

Gastric adenocarcinoma remains a life‑threatening disease, emphasizing the importance of gaining an improved understanding of signaling pathways involved in this disease, which can lead to the development of novel therapeutic methods targeting common molecular pathways shared across different types of gastric adenocarcinoma. The present study revealed phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and aurora kinase A (AURKA) gene alterations, which were involved in changes in the phenotypes of gastric cancer cells, including increased proliferation by cell counting kit‑8 assay and invasion capacity by Transwell invasion assay, and predicted survival rates by KM Plotter database in gastric cancer. The present study investigated the association between PTEN and AURKA. Western blotting revealed that phosphorylated (p)-AURKA correlated with two target genes, PTEN and AURKA. The downregulation of PTEN by small interfering (si)RNA not only increased the expression of AURKA at the mRNA and protein levels by western blotting and by reverse transcription‑quantitative PCR, but also increased the expression of p‑AURKA by western blotting and immunofluorescence analysis. In addition, western blotting and reverse transcription‑quantitative PCR revealed that the downregulation of AURKA affected the expression level of PTEN. Furthermore, PTEN suppressed the malignant phenotypic changes of gastric adenocarcinoma cells by regulating the expression of AURKA inhibited by p‑AURKA, suggesting that p‑AURKA may be the key mediator of the PTEN‑associated activation of AURKA and may be key in maintaining the PTEN‑induced malignant state of gastric adenocarcinoma cells. This hypothesis was confirmed by western blotting, and changes were observed in the protein expression of p‑AURKA and AURKA under conditions in which cells were treated with either MLN8237 or si‑PTEN transfection only, or with si‑PTEN transfection and MLN8237. Knockdown of the expression of PTEN altered the expression of p‑AKT, p‑glycogen synthase kinase 3β and β‑catenin, which are genes that have been reported to be involved in the development of gastric adenocarcinoma. The present study confirmed that p‑AURKA is important in the development of gastric adenocarcinoma and revealed a novel functional link between PTEN, AURKA and p‑AURKA activation. The results also suggest a novel drug design strategy in targeting PTEN and AURKA for more specific gastric cancer cell death that spares normal cells.
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June-2018
Volume 41 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li L, Song Y, Liu Q, Liu X, Wang R, Kang C and Zhang Q: Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA. Int J Mol Med 41: 3629-3641, 2018.
APA
Li, L., Song, Y., Liu, Q., Liu, X., Wang, R., Kang, C., & Zhang, Q. (2018). Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA. International Journal of Molecular Medicine, 41, 3629-3641. https://doi.org/10.3892/ijmm.2018.3544
MLA
Li, L., Song, Y., Liu, Q., Liu, X., Wang, R., Kang, C., Zhang, Q."Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA". International Journal of Molecular Medicine 41.6 (2018): 3629-3641.
Chicago
Li, L., Song, Y., Liu, Q., Liu, X., Wang, R., Kang, C., Zhang, Q."Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA". International Journal of Molecular Medicine 41, no. 6 (2018): 3629-3641. https://doi.org/10.3892/ijmm.2018.3544