Gli2 mediates the development of castration‑resistant prostate cancer

Lu Xia, Hakim Bouamar, Xiang Gu, Carla Zeballos, Tai Qin, Bingzhi Wang, You Zhou, Yuhui Wang, Junhua Yang, Haiyan Zhu, Weishe Zhang, Peter J. Houghton, Lu Zhe Sun

Research output: Contribution to journalArticle

Abstract

Glioma-associated oncogene family zinc finger 2 (Gli2), a key component of the hedgehog signaling pathway, has been previously demonstrated to promote the malignant properties of prostate cancer in vitro. However, the role of Gli2 in the development of castration-resistant prostate cancer (CRPC) has yet to be fully elucidated. In the present study, Gli2 expression was knocked down in androgen-responsive prostate cancer cells using an inducible Gli2 short hairpin RNA. Suppression of Gli2 expression resulted in significant reduction of cell viability, increased the proportion of cells in the G0/G1 phases of the cell cycle and reduced the expression of genes associated with cell cycle progression. Gli2 knockdown sensitized both androgen-dependent and -independent prostate cancer cells to the antiandrogen drug Casodex and prevented the outgrowth of LNCaP prostate cancer cells. In addition, Gli2 knockdown significantly suppressed the development of CRPC in a LNCaP xenograft mouse model, which was reversed by the re-expression of Gli2. In conclusion, to the best of our knowledge, the present study was the first occasion in which the essential role of Gli2 in the development of CRPC was demonstrated, providing a potential therapeutic target for the intervention of CRPC.

Original languageEnglish (US)
Pages (from-to)100-112
Number of pages13
JournalInternational journal of oncology
Volume57
Issue number1
DOIs
StatePublished - Jul 2020

Keywords

  • Castration-resistant prostate cancer
  • Glioma-associated oncogene family zinc finger 2
  • Hedgehog signaling
  • Mouse xenograft
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Xia, L., Bouamar, H., Gu, X., Zeballos, C., Qin, T., Wang, B., Zhou, Y., Wang, Y., Yang, J., Zhu, H., Zhang, W., Houghton, P. J., & Sun, L. Z. (2020). Gli2 mediates the development of castration‑resistant prostate cancer. International journal of oncology, 57(1), 100-112. https://doi.org/10.3892/ijo.2020.5044