Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications
Braz. j. med. biol. res
;
54(6): e10754, 2021. tab, graf
Artigo
em Inglês
| LILACS
| ID: biblio-1285670
ABSTRACT
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.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Neoplasias do Colo do Útero
/
Fosfatidilinositol 3-Quinases
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2021
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
Fundação Oswaldo Cruz/BR
/
Instituto Nacional de Câncer/BR
/
Universidade Federal do Rio de Janeiro/BR
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