Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma cells via the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway

Mol Med Rep. 2015 Jul;12(1):865-70. doi: 10.3892/mmr.2015.3485. Epub 2015 Mar 13.

Abstract

The cell surface glycoprotein Trop2 is overexpressed in various types of epithelial cancer. Laryngeal carcinoma is one of the most common types of head and neck cancer and in a previous study, the expression of Trop2 in laryngeal squamous cell carcinoma (LSCC) was identified as an independent prognostic factor. However, the biological significance of Trop2 in LSCC development remains unclear. In the current study, Trop2 protein expression in fresh LSCC tissue and paracancerous tissue was investigated using western blotting. Trop2 in the Hep2 laryngeal cell line was subsequently suppressed by transfection with small interfering RNA (siRNA). The effects of knockdown of Trop2 on cell viability, migration, invasiveness and ERK/MAPK pathway activity were investigated in the current study. The expression of Trop2 in fresh LSCC tissue was demonstrated to be significantly greater than that in paracancerous tissue. Trop2 expression was also identified to be required for proliferation, migration and invasiveness of Hep2 laryngeal carcinoma cells, as all were blocked by siRNA-mediated Trop2 inhibition. Notably, the ERK/MAPK signaling pathway and cell cycle factor, cyclin D1, were identified to be suppressed following the knockdown of Trop2 in Hep2 cells. These observations suggest that Trop2 serves an oncogenic role in LSCC and has potential as a therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Mitogen-Activated Protein Kinase 1 / biosynthesis
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Neoplasm Invasiveness / genetics
  • Signal Transduction / genetics*

Substances

  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • TACSTD2 protein, human
  • Cyclin D1
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 1