Investigating the role of ITIH5 in the molecular pathogenesis of UV-induced squamous cell carcinoma and its usability for prognosis and therapy

• Applicants: Professor Dr. Edgar Dahl; Dr. Sebastian Huth
• Subject Area: Dermatology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556088964

Although melanoma is the most dangerous tumor type in skin cancer, new studies show that more people worldwide die from the much more common non-melanoma skin cancer, especially cutaneous squamous cell carcinoma. The gene ITIH5 (Inter-alpha-Trypsin Inhibitor Heavy Chain 5), which we first described in the skin in 2015, was recently identified as a putative tumor suppressor gene in melanoma. Although it has also been described as an epigenetically regulated tumor suppressor gene in other tumor entities, its role in the molecular pathogenesis of UV-induced non-melanoma skin cancer has not yet been investigated. In the planned project, we would like to understand the significance of ITIH5 as a possible tumor suppressor gene in squamous cell carcinoma and derive new insights for the therapy and prognosis of this skin cancer variant, which is responsible for the most frequent deaths. Comprehensive in vitro studies will initially investigate the role of ITIH5 in the patho-mechanism of squamous cell carcinoma. Further in vivo UV irradiation experiments with a globally unique Itih5 knockout mouse will deepen these insights, particularly with regard to epigenetic regulation and a possible therapeutic benefit. The usability of ITIH5 as a potential prognostic biomarker in non-melanoma skin cancer will also be evaluated in a clinical trial.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Jens Malte Baron