Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, 200 London Road, Liverpool, L3 9TA, UK.
Department of Oral & Maxillofacial/Head and Neck Surgery, Aintree University Hospital, NHS Foundation Trust, Liverpool, L9 7AL, UK.
Mol Biol Rep. 2020 May;47(5):3987-3992. doi: 10.1007/s11033-020-05381-y. Epub 2020 Mar 31.
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.
iRhom2 是一种无活性的菱形蛋白酶，参与多种信号事件。它与多种癌症类型的发病机制有关，包括食道癌和卵巢癌，而其密切相关的家族成员 iRhom1 则与头颈部癌症有关。然而，iRhom2 在头颈部癌症中的作用尚未得到研究。在 54 例口腔鳞状细胞癌（OSCC）和 24 对配对正常组织中用免疫印迹法检测 iRhom2，结果显示肿瘤组织中 iRhom2 蛋白水平高于正常组织（P<0.05）。iRhom2 的过表达与患者生存不良相关（P<0.0005），但与其他临床病理变量无关。在 OSCC 细胞系中稳定过表达 iRhom2 克隆的情况下观察到细胞迁移增加，而在正常口腔角质形成细胞系 NOK-hTERT 中则没有观察到这种情况，并且通过敲低 iRhom2 可以消除这种情况。在一部分 OSCC 中，iRhom2 蛋白表达增加，这种上调与更快的细胞迁移和患者生存不良有关。这些数据表明 iRhom2 控制的信号事件参与了这种癌症的发病机制。
