RUNX1 promotes MAPK signaling to increase tumor progression and metastasis via OPN in head and neck cancer

Carcinogenesis. 2021 Apr 17;42(3):414-422. doi: 10.1093/carcin/bgaa116.

Abstract

Tumor progression and metastasis are still major burdens for head and neck squamous cell carcinoma (HNSCC). Runt-related transcription factor 1 (RUNX1) is involved in aggressive phenotypes in several cancers, while the molecular role of RUNX1 underlying cancer progression and metastasis of HNSCC remains largely unknown. In our study, RUNX1 expression was increased with disease progression in patients with HNSCC. The silencing of RUNX1 significantly decelerated the malignant progression of HNSCC cells, reduced osteopontin (OPN) expression in vitro and weakened the tumorigenicity of HNSCC cells in vivo. Moreover, we demonstrated that RUNX1 activated the mitogen-activated protein kinase signaling by directly binding to the promoter of OPN in tumor progression and metastasis of HNSCC. Our results may provide new insight into the mechanisms underlying the role of RUNX1 in tumor progression and metastasis and reveal the potential therapeutic target in HNSCC.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / surgery
  • Humans
  • MAP Kinase Signaling System / genetics*
  • Male
  • Mice
  • Middle Aged
  • Osteopontin / genetics*
  • Promoter Regions, Genetic / genetics
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / secondary
  • Squamous Cell Carcinoma of Head and Neck / surgery
  • Xenograft Model Antitumor Assays

Substances

  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human
  • SPP1 protein, human
  • Osteopontin