Glycoprotein NMB promotes tumor formation and malignant progression of laryngeal squamous cell carcinoma

Cancer Sci. 2022 Sep;113(9):3244-3254. doi: 10.1111/cas.15359. Epub 2022 May 18.

Abstract

Laryngeal squamous cell carcinoma (LSCC), although one of the most common head and neck cancers, has a static or slightly decreased survival rate because of difficulties in early diagnosis, lack of effective molecular targeting therapy, and severe dysfunction after radical surgical treatments. Therefore, a novel therapeutic target is crucial to increase treatment efficacy and survival rates in these patients. Glycoprotein NMB (GPNMB), whose role in LSCC remains elusive, is a type 1 transmembrane protein involved in malignant progression of various cancers, and its high expression is thought to be a poor prognostic factor. In this study, we showed that GPNMB expression levels in LSCC samples are significantly higher than those in normal tissues, and GPNMB expression is observed mostly in growth-arrested cancer cells. Furthermore, knockdown of GPNMB reduces monolayer cellular proliferation, cellular migration, and tumorigenic growth, while GPNMB protein displays an inverse relationship with Ki-67 levels. Therefore, we conclude that GPNMB may be an attractive target for future LSCC therapy.

Keywords: cell migration; dormancy; glycoprotein NMB; laryngeal squamous cell carcinoma; tumorigenesis.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / metabolism
  • Head and Neck Neoplasms*
  • Humans
  • Laryngeal Neoplasms* / genetics
  • Laryngeal Neoplasms* / pathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • MicroRNAs*
  • Promoter Regions, Genetic
  • Squamous Cell Carcinoma of Head and Neck
  • Transcription Factors / metabolism

Substances

  • GPNMB protein, human
  • Glycoproteins
  • Membrane Glycoproteins
  • MicroRNAs
  • Transcription Factors