TRAF2 and FKBP51 as possible markers for identification of suitable melanoma tumors for tumor necrosis factor-α inhibition
| Autor: | Stefania Staibano, Maria Fiammetta Romano, Martina Tufano, Gennaro Ilardi, Anna Rea, Paolo D'Arrigo, Francesco Merolla, Simona Romano, Antonello Petrella |
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| Přispěvatelé: | Romano, Simona, D'Arrigo, Paolo, Tufano, Martina, Staibano, Stefania, Rea, Anna, Merolla, Francesco, Ilardi, Gennaro, Petrella, Antonello, Romano, Maria F |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research TRAF2 Skin Neoplasms medicine.medical_treatment nuclear factor-κB Dermatology IκB kinase Cell Line Tacrolimus Binding Proteins 03 medical and health sciences 0302 clinical medicine tumor necrosis factor receptor-Associated factor 2 Cell Line Tumor medicine Humans Melanoma Tumor Chemistry FK506-binding protein 51 tumor necrosis factor-α Biomarkers TNF Receptor-Associated Factor 2 medicine.disease 030104 developmental biology Cytokine Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Tumor necrosis factor alpha |
| Popis: | Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine, whose role in melanoma is controversial. Although high-dose TNF-α is approved for the treatment of patients with in transit-metastatic melanoma confined to the limb, diverse preclinical models of melanoma have shown that TNF-α can induce cell invasion. Biomarkers that can differentiate between the dual role of TNF-α are needed. TRAF2 is critical to TNF receptor-induced activation of nuclear factor-κB (NF-κB), allowing shifting from death to survival-signaling cascades. The large immunophilin FKBP51 acts as a scaffold and catalyst in the IκB kinase complex assembly and activation. Here, using microscopy and an electrophoretic mobility-shift assay, we provide further evidence in support of the essential role of FKBP51 in sustaining the TNF-α NF-κB signaling in melanoma. Through the cross-linking reaction with the chemical linker disuccinimidyl glutarate, we show that a direct interaction occurs between FKBP51 and TRAF2 in melanoma cells. Immunohistochemistry of tumor samples from 24 patients with cutaneous melanomas showed a correlation between the expressions of the two proteins. Given the association of FKBP51 and TRAF2 with TNF-α-induced NF-κB signaling and their correlation in tumor samples, we propose that the two proteins can be exploited as useful markers for the identification of those melanoma tumors that can benefit from TNF-α inhibition. Future studies will address this hypothesis. |
| Databáze: | OpenAIRE |
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