iRhom2 in the pathogenesis of oral squamous cell carcinoma

Mol Biol Rep. 2020 May;47(5):3987-3992. doi: 10.1007/s11033-020-05381-y. Epub 2020 Mar 31.

Abstract

iRhom2 is an inactive rhomboid protease involved in diverse signalling events. It has been implicated in the pathogenesis of a number of cancer types, including oesophageal and ovarian cancer, while its closely associated family member, iRhom1, is implicated in head and neck cancer. However, a role for iRhom2 in head and neck cancer has not been investigated. Immunoblotting for iRhom2 in 54 oral squamous cell carcinoma (OSCC) and 24 paired normal tissues demonstrated higher levels of iRhom2 protein in tumour compared with normal samples (P < 0.05). iRhom2 over-expression correlated with poor patient survival (P < 0.0005) but with no other clinicopathological variable. Increased cell migration was observed in stably over-expressing iRhom2 clones of OSCC cell lines in the absence of increased cell proliferation, but not in the normal oral keratinocyte cell line, NOK-hTERT, and this was abrogated by knock-down of iRhom2. iRhom2 protein expression is increased in a proportion of OSCC and this up-regulation is associated with faster cell migration and decreased patient survival. These data implicate iRhom2-controlled signalling events in the pathogenesis of this cancer.

Keywords: Cell migration; Head and neck squamous cell carcinoma; Oral squamous cell carcinoma; iRhom2.

MeSH terms

  • ADAM17 Protein / genetics
  • ADAM17 Protein / metabolism
  • Carrier Proteins / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kaplan-Meier Estimate
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • RHBDF2 protein, human
  • ADAM17 Protein