PMID- 30451787
OWN - NLM
STAT- MEDLINE
DCOM- 20190614
LR  - 20190614
IS  - 1473-5636 (Electronic)
IS  - 0960-8931 (Linking)
VI  - 29
IP  - 2
DP  - 2019 Apr
TI  - TRAF2 and FKBP51 as possible markers for identification of suitable melanoma 
      tumors for tumor necrosis factor-alpha inhibition.
PG  - 145-150
LID - 10.1097/CMR.0000000000000553 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine, whose role in melanoma 
      is controversial. Although high-dose TNF-alpha 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-alpha can induce cell invasion. 
      Biomarkers that can differentiate between the dual role of TNF-alpha are needed. 
      TRAF2 is critical to TNF receptor-induced activation of nuclear factor-kappaB 
      (NF-kappaB), allowing shifting from death to survival-signaling cascades. The large 
      immunophilin FKBP51 acts as a scaffold and catalyst in the IkappaB 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-alpha NF-kappaB 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-alpha-induced NF-kappaB 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-alpha inhibition. Future studies will address this hypothesis.
FAU - Romano, Simona
AU  - Romano S
AD  - Department of Molecular Medicine and Medical Biotechnologies.
FAU - D'Arrigo, Paolo
AU  - D'Arrigo P
AD  - Department of Molecular Medicine and Medical Biotechnologies.
FAU - Tufano, Martina
AU  - Tufano M
AD  - Department of Molecular Medicine and Medical Biotechnologies.
FAU - Staibano, Stefania
AU  - Staibano S
AD  - Department of Advanced Biomedical Sciences, Federico II University, Naples.
FAU - Rea, Anna
AU  - Rea A
AD  - Department of Molecular Medicine and Medical Biotechnologies.
FAU - Merolla, Francesco
AU  - Merolla F
AD  - Department of Medicine and Health Science 'V. Tiberio', University of Molise, 
      Campobasso.
FAU - Ilardi, Gennaro
AU  - Ilardi G
AD  - Department of Advanced Biomedical Sciences, Federico II University, Naples.
FAU - Petrella, Antonello
AU  - Petrella A
AD  - Department of Pharmacy, University of Salerno, Fisciano, Italy.
FAU - Romano, Maria F
AU  - Romano MF
AD  - Department of Molecular Medicine and Medical Biotechnologies.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Melanoma Res
JT  - Melanoma research
JID - 9109623
RN  - 0 (Biomarkers)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - EC 5.2.1.- (Tacrolimus Binding Proteins)
RN  - EC 5.2.1.8 (tacrolimus binding protein 5)
SB  - IM
MH  - Biomarkers/*chemistry
MH  - Cell Line, Tumor
MH  - Humans
MH  - Melanoma/*genetics/metabolism/pathology
MH  - Skin Neoplasms/*genetics/metabolism/pathology
MH  - TNF Receptor-Associated Factor 2/*metabolism
MH  - Tacrolimus Binding Proteins/*metabolism
EDAT- 2018/11/20 06:00
MHDA- 2019/06/15 06:00
CRDT- 2018/11/20 06:00
PHST- 2018/11/20 06:00 [pubmed]
PHST- 2019/06/15 06:00 [medline]
PHST- 2018/11/20 06:00 [entrez]
AID - 10.1097/CMR.0000000000000553 [doi]
PST - ppublish
SO  - Melanoma Res. 2019 Apr;29(2):145-150. doi: 10.1097/CMR.0000000000000553.