Interaction of Integrin αvβ8 With Type I Collagen Promotes Squamous Cell Carcinoma Cell Motility via RAC1 Activation

Anticancer Res. 2023 Nov;43(11):4833-4841. doi: 10.21873/anticanres.16680.

Abstract

Background/aim: The interaction of integrin αvβ8 with type I collagen was shown to promote oral squamous cell carcinoma (SCC) cell proliferation via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. However, the role of integrin αvβ8 in SCC progression remains poorly understood. In this study, the role of integrin αvβ8 in oral SCC progression was therefore investigated.

Materials and methods: Integrin αv and β8 protein expression in oral SCC cells was examined by western blotting. Oral SCC cell motility was investigated using modified Boyden chamber assays. Behavior of oral SCC cells was examined in three-dimensional culture using type I collagen gel. Ras homolog family member A (RHOA), Ras-related C3 botulinum toxin substrate 1 (RAC1), and cell division control protein 42 homolog (CDC42) activity of oral SCC cells was analyzed by pull-down assays.

Results: SCC cells with high integrin αvβ8 expression levels had a high ability to migrate on type I collagen and exhibited enhanced invasion into type I collagen gel. In SCC cells with high integrin αvβ8 expression level, cultivation on type I collagen induced RAC1 activation. Treatment with RAC1 inhibitor reduced type I collagen-induced motility of SCC cells. Down-regulation of integrin β8 by specific antisense oligonucleotide reduced type I collagen-induced RAC1 activation and suppressed cell motility and invasion into type I collagen gel.

Conclusion: The interaction of integrin αvβ8 with type I collagen facilitates SCC cell motility and invasion via RAC1 activation. Therefore, integrin αvβ8 and RAC1 may represent new targets for inhibiting metastasis and invasion in patients with oral SCC.

Keywords: Integrin αvβ8; RAC1 signaling pathway; cell motility; invasion; squamous cell carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell*
  • Cell Movement
  • Collagen Type I
  • Extracellular Signal-Regulated MAP Kinases
  • Head and Neck Neoplasms*
  • Humans
  • Integrin alphaV
  • Mouth Neoplasms*
  • Squamous Cell Carcinoma of Head and Neck
  • rac1 GTP-Binding Protein

Substances

  • Collagen Type I
  • Extracellular Signal-Regulated MAP Kinases
  • integrin alphavbeta8
  • rac1 GTP-Binding Protein
  • RAC1 protein, human
  • ITGB8 protein, human
  • Integrin alphaV