Angiomotin-like 1 plays a tumor-promoting role in glioma by enhancing the activation of YAP1 signaling

Environ Toxicol. 2021 Dec;36(12):2500-2511. doi: 10.1002/tox.23363. Epub 2021 Sep 4.

Abstract

Angiomotin-like 1 (AMOTL1) is reportedly a pivotal tumor-associated protein that is strongly associated with the tumorigenesis of multiple malignant tumors. However, the issue of whether AMOTL1 plays a role in the tumorigenesis of glioma remains unclear. The aim of this work was to explore the possible relationship between AMOTL1 and glioma progression. Results demonstrated that high levels of AMOTL1 in glioma tissues were associated with a reduced survival rate in patients with glioma. Cellular functional assays revealed that silencing of AMOTL1 in glioma cell lines substantially decreased cell proliferation and invasion and increased cell apoptosis. Further investigation revealed that silencing of AMOTL1 inhibited the activation of yes-associated protein 1 (YAP1) and decreased the expression of YAP1 target genes. Reactivation of YAP1 reversed AMOTL1-silencing-induced antitumor effects, whereas inhibition of YAP1 abolished AMOTL1-overexpression-induced tumor-promoting effects in glioma cells. Silencing of AMOTL1 also retarded the growth of glioma cell-derived xenograft tumors in vivo. In conclusion, these findings suggested that AMOTL1 may exert a tumor-promoting function in glioma by enhancing the activation of YAP1 signaling. This work suggested AMOTL1 as a potential target for the development of antiglioma therapy.

Keywords: AMOTL1; YAP1; glioma.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Angiomotins
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Glioma* / genetics
  • Humans
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins
  • Signal Transduction*
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins

Substances

  • AMOTL1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Angiomotins
  • Membrane Proteins
  • Neoplasm Proteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human