A Role for Proteomics in Identifying Targets for Radiosensitizing Strategies in Melanoma: The FKBP51 Paradigm*Corresponding Author: Simona Romano PhD, Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Pansini, 5 -80131-Naples, Italy, Tel: +39/0817463123, Fax: +39/0817463205, Email: [email protected], [email protected]
Received Date: May 27, 2014 / Accepted Date: Jul 28, 2014 / Published Date: Aug 01, 2014
Citation: D’Angelillo A, Pacelli R, Martinelli R, D’Arrigo P, Staibano S, et al.(2014) A Role for Proteomics in Identifying Targets for Radiosensitizing Strategies in Melanoma: The FKBP51 Paradigm. J Proteomics Bioinform 7:240-247.DOI: 10.4172/jpb.1000325
Copyright: © 2014 D’Angelillo A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
The treatment of metastatic melanoma is challenging and in the vast majority of cases unsuccessful. Melanoma cells are resistant to most standard therapeutics. We have recently demonstrated that FKBP51 regulates melanoma response to ionizing radiation (IR). To find out molecular targets for radiosensitizing strategies to apply in this neoplasm, we investigated the changes of protein profiles in irradiated melanoma depleted or not of FKBP51, by protein microarray approach. Among the multiple molecules that were found modulated in our cell model, the decrease of several pPKC isoforms in the FKBP51-depleted (IR-sensitive) melanoma appeared to us particularly interesting, because PKC is involved in radiation response. Therefore, PKC was chosen for further investigation. After validating by western blot proteomics results, we found that targeting PKC, with the pan PKC inhibitor LY317615 or enzastaurin, significantly enhanced IR-induced cell death. Most interestingly, enzastaurin combined with IR appeared to be effective in eliminating a subset of melanoma cells expressing a stemness marker. Our study highlighted a role for proteomics in finding useful targets to overcome melanoma resistance, and suggested a combination treatment, which deserves to be investigated in a clinical setting.