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Updated: Dec 25, 2025

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
iRhom2 in the pathogenesis of oral squamous cell carcinoma
Matthew E Agwae1, Richard J Shaw1,2, Asterios Triantafyllou3
1Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, 200 London Road, Liverpool, L3 9TA, UK.
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.
Insights
iRhom2 protein is elevated in oral squamous cell carcinoma (OSCC), correlating with increased cell migration and poorer patient survival. This suggests iRhom2 plays a role in OSCC development.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- iRhom2 is an inactive rhomboid protease implicated in various signaling pathways and cancer pathogenesis.
- While iRhom1 is linked to head and neck cancer, iRhom2's role in this specific cancer type remains unexplored.
Purpose of the Study:
- To investigate the role of iRhom2 in the development of oral squamous cell carcinoma (OSCC).
- To determine the correlation between iRhom2 expression, clinicopathological features, and patient survival in OSCC.
Main Methods:
- Immunoblotting was used to quantify iRhom2 protein levels in 54 OSCC tissues and 24 paired normal tissues.
- OSCC cell lines with stable iRhom2 overexpression and knock-down were utilized to assess cell migration and proliferation.
- Correlation analysis was performed between iRhom2 expression and patient survival and clinicopathological variables.
Main Results:
- iRhom2 protein levels were significantly higher in OSCC tumors compared to normal tissues (P < 0.05).
- Overexpression of iRhom2 correlated strongly with decreased patient survival (P < 0.0005) but not with other clinicopathological variables.
- iRhom2 overexpression enhanced cell migration in OSCC cell lines without affecting proliferation, an effect reversed by iRhom2 knock-down.
Conclusions:
- iRhom2 protein expression is upregulated in a subset of OSCC.
- Increased iRhom2 is associated with enhanced cancer cell migration and reduced patient survival in OSCC.
- These findings suggest iRhom2-mediated signaling is involved in OSCC pathogenesis and may represent a therapeutic target.
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