Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells

S. Romano, A. D'Angelillo, R. Pacelli, S. Staibano, E. De Luna, R. Bisogni, E. L. Eskelinen, M. Mascolo, G. Cal, C. Arra, M. F. Romano

Research output: Contribution to journalArticle

Abstract

FK506-binding protein 51 (FKBP51) is an immunophilin with isomerase activity, which performs important biological functions in the cell. It has recently been involved in the apoptosis resistance of malignant melanoma. The aim of this study was to investigate the possible role of FKBP51 in the control of response to ionizing radiation (Rx) in malignant melanoma. FKBP51-silenced cells showed reduced clonogenic potential after irradiation compared with non-silenced cells. After Rx, we observed apoptosis in FKBP51-silenced cells and autophagy in non-silenced cells. The FKBP51-controlled radioresistance mechanism involves NF-B. FKBP51 was required for the activation of Rx-induced NF-B, which in turn inhibited apoptosis by stimulating X-linked inhibitor of apoptosis protein and promoting authophagy-mediated Bax degradation. Using a tumor-xenograft mouse model, the in vivo pretreatment of tumors with FKBP51-siRNA provoked massive apoptosis after irradiation. Immunohistochemical analysis of 10 normal skin samples and 80 malignant cutaneous melanomas showed that FKBP51 is a marker of melanocyte malignancy, correlating with vertical growth phase and lesion thickness. Finally, we provide evidence that FKBP51 targeting radiosensitizes cancer stem/initiating cells. In conclusion, our study identifies a possible molecular target for radiosensitizing therapeutic strategies against malignant melanoma.

Original languageEnglish
Pages (from-to)145-157
Number of pages13
JournalCell Death and Differentiation
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • apoptosis
  • autophagy
  • FKBP51
  • melanoma
  • NF-κB

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells'. Together they form a unique fingerprint.

  • Cite this

    Romano, S., D'Angelillo, A., Pacelli, R., Staibano, S., De Luna, E., Bisogni, R., Eskelinen, E. L., Mascolo, M., Cal, G., Arra, C., & Romano, M. F. (2010). Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells. Cell Death and Differentiation, 17(1), 145-157. https://doi.org/10.1038/cdd.2009.115