High expression of Notch2 drives tongue squamous cell carcinoma carcinogenesis

Exp Cell Res. 2021 Feb 1;399(1):112452. doi: 10.1016/j.yexcr.2020.112452. Epub 2020 Dec 28.

Abstract

Tongue squamous cell carcinoma (TSCC) is one of the most common cancers in the oral cavity. Notch signaling is frequently dysregulated in cancer. However, the role of Notch2 in TSCC is not well understood. The aim of this study was to investigate the effect of abnormal expression of Notch2 in TSCC. The expression of Notch2 was tested in 47 pairs of tissues from tongue cancer and normal samples by using immunohistochemical staining. Tongue cancer cells were transfected with siRNA or plasmid. The proliferation of the cells was tested by the CCK8 assay and colony formation assay. Subcutaneous tumor model was established to observe tumor growth. Transwell assay was used to detect the changes of cell migration and invasion ability. A humanized anti-Notch2 antibody was used to TSCC cells. We found that Notch2 was upregulated in tongue carcinoma tissues. Knocking down the expression of Notch2 by siRNA in the TSCC cell lines decreased proliferation ability both in vitro and in vivo. In addition, migration and invasion abilities were inhibited by knockdown of Notch2 in the TSCC cells. However, overexpression of Notch2 increased tongue cancer cell proliferation, invasion and migration. The humanized anti-Notch2 antibody inhibited TSCC cell growth. The results indicated that Notch2 is an oncogene in tongue squamous cell carcinoma and may become the target of a new approach for treating TSCC.

Keywords: Invasion; Migration; Notch signaling pathway; Proliferation; Tongue squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Receptor, Notch2 / genetics*
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology
  • Up-Regulation / genetics

Substances

  • NOTCH2 protein, human
  • Receptor, Notch2