FOLR1-stabilized β-catenin promotes laryngeal carcinoma progression through EGFR/AKT/GSK-3β pathway

Mol Carcinog. 2024 Jan;63(1):34-44. doi: 10.1002/mc.23634. Epub 2023 Sep 13.

Abstract

Folate receptor 1 (FOLR1) is overexpressed in numerous epithelial malignancies; however, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. In the present study, we demonstrated that FOLR1 messenger RNA and protein expression levels were higher in LSCC tissues than in the adjacent normal tissues. Additionally, FOLR1 promoted the proliferation and migration of LSCC cells, whereas small interfering RNA-mediated knockdown of β-catenin abolished these effects. Moreover, FOLR1 stabilizes β-catenin by inhibiting its ubiquitination and degradation. Furthermore, blocking the interaction between epidermal growth factor receptor (EGFR) and the EGFR/AKT/glycogen synthase (GSK)3β signaling axis both abolished FOLR1's effects on the expression and nuclear aggregation of β-catenin. In summary, our work reveals a novel mode in which FOLR1 promotes the proliferation and migration of LSCC by enhancing the stability and nuclear translocation of β-catenin through the EGFR/AKT/GSK3β axis.

Keywords: EGFR; FOLR1; laryngeal carcinoma; ubiquitination; β-catenin.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Folate Receptor 1
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Head and Neck Neoplasms*
  • Humans
  • Proto-Oncogene Proteins c-akt / metabolism
  • Squamous Cell Carcinoma of Head and Neck
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3 beta
  • Folate Receptor 1
  • ErbB Receptors
  • FOLR1 protein, human
  • EGFR protein, human