COVID‑19 and SARS‑CoV‑2 host cell entry mediators: Expression profiling of TMRSS4 in health and disease

Katopodis,Periklis; Kerslake,Rachel; Davies,Julie; Randeva,Harpal S.; Chatha,Kamaljit; Hall,Marcia; Spandidos,Demetrios A.; Anikin,Vladimir; Polychronis,Andreas; Robertus,Jan L.; Kyrou,Ioannis; Karteris,Emmanouil

doi:10.3892/ijmm.2021.4897

COVID‑19 and SARS‑CoV‑2 host cell entry mediators: Expression profiling of TMRSS4 in health and disease

Authors:
- Periklis Katopodis
- Rachel Kerslake
- Julie Davies
- Harpal S. Randeva
- Kamaljit Chatha
- Marcia Hall
- Demetrios A. Spandidos
- Vladimir Anikin
- Andreas Polychronis
- Jan L. Robertus
- Ioannis Kyrou
- Emmanouil Karteris
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Affiliations: Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK, Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK, Laboratory of Clinical Virology, Medical School, University of Crete, 71409 Heraklion, Greece, Mount Vernon Cancer Centre, Middlesex HA6 2RN, UK, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
Published online on: February 26, 2021 https://doi.org/10.3892/ijmm.2021.4897
Article Number: 64
Copyright: © Katopodis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Severe acute respiratory syndrome (SARS) coronavirus‑2 (SARS‑CoV‑2), the causative viral agent for the ongoing COVID‑19 pandemic, enters its host cells primarily via the binding of the SARS‑CoV‑2 spike (S) proteins to the angiotensin‑converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin‑1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS‑CoV‑2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using in silico tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID‑19 symptomatology as another SARS‑CoV‑2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.

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