Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications
Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), ca...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/pdf/bjmbr/v54n6/1414-431X-bjmbr-54-6-e10754.pdf |
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| author | F.G. Gomes V.H. Almeida K. Martins-Cardoso M.M.D.C. Martins-Dinis A.M.R. Rondon A.C. de Melo T.M. Tilli R.Q. Monteiro |
| author_facet | F.G. Gomes V.H. Almeida K. Martins-Cardoso M.M.D.C. Martins-Dinis A.M.R. Rondon A.C. de Melo T.M. Tilli R.Q. Monteiro |
| author_sort | F.G. Gomes |
| collection | DOAJ |
| description | Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model. |
| first_indexed | 2024-12-22T01:19:27Z |
| format | Article |
| id | doaj.art-c70207c8093d4a748ecd717bb5d0d810 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-12-22T01:19:27Z |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-c70207c8093d4a748ecd717bb5d0d8102022-12-21T18:43:46ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X10.1590/1414-431x202010754Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implicationsF.G. GomesV.H. AlmeidaK. Martins-CardosoM.M.D.C. Martins-DinisA.M.R. RondonA.C. de MeloT.M. TilliR.Q. MonteiroEpidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.http://www.scielo.br/pdf/bjmbr/v54n6/1414-431X-bjmbr-54-6-e10754.pdfCervical cancerEpidermal growth factor receptorUrokinase-type plasminogen activatorThrombomodulinFibrinolytic system |
| spellingShingle | F.G. Gomes V.H. Almeida K. Martins-Cardoso M.M.D.C. Martins-Dinis A.M.R. Rondon A.C. de Melo T.M. Tilli R.Q. Monteiro Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications Brazilian Journal of Medical and Biological Research Cervical cancer Epidermal growth factor receptor Urokinase-type plasminogen activator Thrombomodulin Fibrinolytic system |
| title | Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications |
| title_full | Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications |
| title_fullStr | Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications |
| title_full_unstemmed | Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications |
| title_short | Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications |
| title_sort | epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer functional and prognostic implications |
| topic | Cervical cancer Epidermal growth factor receptor Urokinase-type plasminogen activator Thrombomodulin Fibrinolytic system |
| url | http://www.scielo.br/pdf/bjmbr/v54n6/1414-431X-bjmbr-54-6-e10754.pdf |
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