Open Access

GASC1 promotes glioma progression by enhancing NOTCH1 signaling

  • Authors:
    • Zhengzheng Xiao
    • Xiaoli Yang
    • Zebin Liu
    • Zheng Shao
    • Chaojun  Song
    • Kun Zhang
    • Xiaobin Wang
    • Zhengwei Li
  • View Affiliations

  • Published online on: February 28, 2021     https://doi.org/10.3892/mmr.2021.11949
  • Article Number: 310
  • Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent studies have reported that gene amplified in squamous cell carcinoma 1 (GASC1) is involved in the progression of several types of cancer. However, whether GASC1 promotes glioma progression remains unknown. Therefore, the present study aimed to investigate the effect of GASC1 exposure on glioma tumorigenesis. The western blot demonstrated that grade III and IV glioma tissues exhibited a higher mRNA and protein expression of GASC1. Moreover, CD133+ U87 or U251 cells from magnetic cell separation exhibited a higher GASC1 expression. Invasion Transwell assay, clonogenic assay and wound healing assay have shown that GASC1 inhibition using a pharmacological inhibitor and specific short hairpin (sh)RNA suppressed the invasive, migratory and tumorsphere forming abilities of primary culture human glioma cells. Furthermore, GASC1‑knockdown decreased notch receptor (Notch) responsive protein hes family bHLH transcription factor 1 (Hes1) signaling. GASC1 inhibition reduced notch receptor 1 (NOTCH1) expression, and a NOTCH1 inhibitor enhanced the effects of GASC1 inhibition on the CD133+ U87 or U251 cell tumorsphere forming ability, while NOTCH1 overexpression abrogated these effects. In addition, the GASC1 inhibitor caffeic acid and/or the NOTCH1 inhibitor DAPT (a γ‑Secretase Inhibitor), efficiently suppressed the human glioma xenograft tumors. Thus, the present results demonstrated the importance of GASC1 in the progression of glioma and identified that GASC1 promotes glioma progression, at least in part, by enhancing NOTCH signaling, suggesting that GASC1/NOTCH1 signaling may be a potential therapeutic target for glioma treatment.
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May-2021
Volume 23 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Xiao Z, Yang X, Liu Z, Shao Z, Song C, Zhang K, Wang X and Li Z: GASC1 promotes glioma progression by enhancing NOTCH1 signaling. Mol Med Rep 23: 310, 2021
APA
Xiao, Z., Yang, X., Liu, Z., Shao, Z., Song, C., Zhang, K. ... Li, Z. (2021). GASC1 promotes glioma progression by enhancing NOTCH1 signaling. Molecular Medicine Reports, 23, 310. https://doi.org/10.3892/mmr.2021.11949
MLA
Xiao, Z., Yang, X., Liu, Z., Shao, Z., Song, C., Zhang, K., Wang, X., Li, Z."GASC1 promotes glioma progression by enhancing NOTCH1 signaling". Molecular Medicine Reports 23.5 (2021): 310.
Chicago
Xiao, Z., Yang, X., Liu, Z., Shao, Z., Song, C., Zhang, K., Wang, X., Li, Z."GASC1 promotes glioma progression by enhancing NOTCH1 signaling". Molecular Medicine Reports 23, no. 5 (2021): 310. https://doi.org/10.3892/mmr.2021.11949