FKBP51 increases the tumour‐promoter potential of TGF‐beta
Abstract Background FKBP51 (FKBP5 Official Symbol) is a large molecular weight component of the family of FK506 binding proteins (FKBP). In recent years, research studies from our laboratory highlighted functions for FKBP51 in the control of apoptosis and melanoma progression. FKBP51 expression corr...
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| Format: | Article |
| Language: | English |
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Wiley
2014-12-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1186/2001-1326-3-1 |
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| author | Simona Romano Anna D’Angelillo Paolo D’Arrigo Stefania Staibano Adelaide Greco Arturo Brunetti Massimiliano Scalvenzi Rita Bisogni Iris Scala Maria Fiammetta Romano |
| author_facet | Simona Romano Anna D’Angelillo Paolo D’Arrigo Stefania Staibano Adelaide Greco Arturo Brunetti Massimiliano Scalvenzi Rita Bisogni Iris Scala Maria Fiammetta Romano |
| author_sort | Simona Romano |
| collection | DOAJ |
| description | Abstract Background FKBP51 (FKBP5 Official Symbol) is a large molecular weight component of the family of FK506 binding proteins (FKBP). In recent years, research studies from our laboratory highlighted functions for FKBP51 in the control of apoptosis and melanoma progression. FKBP51 expression correlated with the invasiveness and aggressiveness of melanoma. Since a role for TGF‐β in the enhanced tumorigenic potential of melanoma cells is widely described, we hypothesized a cooperative effect between FKBP51 and TGF‐β in melanoma progression. Methods SAN and A375 melanoma cell lines were utilized for this study. Balb/c IL2γ NOD SCID served to assess the ability to colonize organs and metastasize of different cell lines, which was evaluated by in vivo imaging. Realtime PCR and western blot served for measurement of mRNA and protein expression, respectively. Results By comparing the metastatic potential of two melanoma cell lines, namely A375 and SAN, we confirmed that an increased capability to colonize murine organs was associated with increased levels of FKBP51. A375 melanoma cell line expressed FKBP51 mRNA levels 30‐fold higher in comparison to the SAN mRNA level and appeared more aggressive than SAN melanoma cell line in an experimental metastasis model. In addition, A375 expressed, more abundantly than SAN, the TGF‐β and the pro angiogenic TGF‐β receptor type III (TβRIII) factors. FKBP51 silencing produced a reduction of TGF‐β and TβRIII gene expression in A375 cell line, in accordance with previous studies. We found that the inducing effect of TGF‐β on Sparc and Vimentin expression was impaired in condition of FKBP51 depletion, suggesting that FKBP51 is an important cofactor in the TGF‐β signal. Such a hypothesis was supported by co immunoprecipitation assays, showing that FKBP51 interacted with either Smad2,3 and p300. In normal melanocytes, FKBP51 potentiated the effect of TGF‐β on N‐cadherin expression and conferred a mesenchymal‐like morphology to such round‐shaped cells. Conclusions Overall, our findings show that FKBP51 enhances some pro oncogenic functions of TGF‐β, suggesting that FKBP51‐overexpression may help melanoma to take advantage of the tumor promoting activities of the cytokine. |
| first_indexed | 2024-12-13T06:42:04Z |
| format | Article |
| id | doaj.art-065552bab03d45b583756d57ecef83dc |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-13T06:42:04Z |
| publishDate | 2014-12-01 |
| publisher | Wiley |
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| series | Clinical and Translational Medicine |
| spelling | doaj.art-065552bab03d45b583756d57ecef83dc2022-12-21T23:56:24ZengWileyClinical and Translational Medicine2001-13262014-12-0131n/an/a10.1186/2001-1326-3-1FKBP51 increases the tumour‐promoter potential of TGF‐betaSimona Romano0Anna D’Angelillo1Paolo D’Arrigo2Stefania Staibano3Adelaide Greco4Arturo Brunetti5Massimiliano Scalvenzi6Rita Bisogni7Iris Scala8Maria Fiammetta Romano9Department of Molecular Medicine and Medical BiotechnologiesFederico II University80131via Pansini, Naples 5ItalyDepartment of Advanced Biomedical SciencesFederico II UniversityNaplesItalyDepartment of Molecular Medicine and Medical BiotechnologiesFederico II University80131via Pansini, Naples 5ItalyDepartment of Advanced Biomedical SciencesFederico II UniversityNaplesItalyDepartment of Advanced Biomedical SciencesFederico II UniversityNaplesItalyDepartment of Advanced Biomedical SciencesFederico II UniversityNaplesItalyDepartment of Clinical Medicine and SurgeryDermatology SectionUniversity Federico II of NaplesNaplesItalyDepartment of Molecular Medicine and Medical BiotechnologiesFederico II University80131via Pansini, Naples 5ItalyDepartment of Medical and Translational SciencesPediatrics SectionUniversity Federico II of NaplesNaplesItalyDepartment of Molecular Medicine and Medical BiotechnologiesFederico II University80131via Pansini, Naples 5ItalyAbstract Background FKBP51 (FKBP5 Official Symbol) is a large molecular weight component of the family of FK506 binding proteins (FKBP). In recent years, research studies from our laboratory highlighted functions for FKBP51 in the control of apoptosis and melanoma progression. FKBP51 expression correlated with the invasiveness and aggressiveness of melanoma. Since a role for TGF‐β in the enhanced tumorigenic potential of melanoma cells is widely described, we hypothesized a cooperative effect between FKBP51 and TGF‐β in melanoma progression. Methods SAN and A375 melanoma cell lines were utilized for this study. Balb/c IL2γ NOD SCID served to assess the ability to colonize organs and metastasize of different cell lines, which was evaluated by in vivo imaging. Realtime PCR and western blot served for measurement of mRNA and protein expression, respectively. Results By comparing the metastatic potential of two melanoma cell lines, namely A375 and SAN, we confirmed that an increased capability to colonize murine organs was associated with increased levels of FKBP51. A375 melanoma cell line expressed FKBP51 mRNA levels 30‐fold higher in comparison to the SAN mRNA level and appeared more aggressive than SAN melanoma cell line in an experimental metastasis model. In addition, A375 expressed, more abundantly than SAN, the TGF‐β and the pro angiogenic TGF‐β receptor type III (TβRIII) factors. FKBP51 silencing produced a reduction of TGF‐β and TβRIII gene expression in A375 cell line, in accordance with previous studies. We found that the inducing effect of TGF‐β on Sparc and Vimentin expression was impaired in condition of FKBP51 depletion, suggesting that FKBP51 is an important cofactor in the TGF‐β signal. Such a hypothesis was supported by co immunoprecipitation assays, showing that FKBP51 interacted with either Smad2,3 and p300. In normal melanocytes, FKBP51 potentiated the effect of TGF‐β on N‐cadherin expression and conferred a mesenchymal‐like morphology to such round‐shaped cells. Conclusions Overall, our findings show that FKBP51 enhances some pro oncogenic functions of TGF‐β, suggesting that FKBP51‐overexpression may help melanoma to take advantage of the tumor promoting activities of the cytokine.https://doi.org/10.1186/2001-1326-3-1MelanomaTGF‐βFKBP51Metastasis |
| spellingShingle | Simona Romano Anna D’Angelillo Paolo D’Arrigo Stefania Staibano Adelaide Greco Arturo Brunetti Massimiliano Scalvenzi Rita Bisogni Iris Scala Maria Fiammetta Romano FKBP51 increases the tumour‐promoter potential of TGF‐beta Clinical and Translational Medicine Melanoma TGF‐β FKBP51 Metastasis |
| title | FKBP51 increases the tumour‐promoter potential of TGF‐beta |
| title_full | FKBP51 increases the tumour‐promoter potential of TGF‐beta |
| title_fullStr | FKBP51 increases the tumour‐promoter potential of TGF‐beta |
| title_full_unstemmed | FKBP51 increases the tumour‐promoter potential of TGF‐beta |
| title_short | FKBP51 increases the tumour‐promoter potential of TGF‐beta |
| title_sort | fkbp51 increases the tumour promoter potential of tgf beta |
| topic | Melanoma TGF‐β FKBP51 Metastasis |
| url | https://doi.org/10.1186/2001-1326-3-1 |
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