Por favor, use este identificador para citar o enlazar este ítem:https://uvadoc.uva.es/handle/10324/47000
Título
Secreted PLA2 induces proliferation in astrocytoma through the EGF receptor: another inflammation-cancer link
Autor
Año del Documento
2010
Editorial
Oxford University Press
Descripción
Producción Científica
Documento Fuente
Neuro-Oncology, 2010, vol. 12, n. 10. p. 1014-1023
Resumo
We have investigated mechanisms that contribute to reinforce the relationship between inflammation and cancer. Secreted phospholipase A2 group IIA (sPLA2-IIA) is a molecule relevant in inflammatory events and has been proposed as a marker for some of these. Previously, we reported the mitogenic properties of this sPLA2 in the human astrocytoma cell line 1321N1. Here, we go deeper into the mechanisms that link this inflammatory protein with proliferation in one of the most aggressive types of tumors. We found that phosphorylation of the extracellular regulated kinase (ERK) was preceded by the activation of the small GTPase Ras, and both failed to be activated by inhibiting protein kinase C (PKC). Fractionation and immunofluorescence studies revealed translocation of PKC alpha, delta, and epsilon to the membrane fraction upon stimulation with sPLA2-IIA. Immunoprecipitation analysis showed that sPLA2-IIA induces phosphorylation of the epidermal growth factor receptor (EGFR) through a PKC-dependent pathway. We found that phosphorylation of this receptor contributed to Ras and ERK activation and that inhibition of ERK, PKC, and EGFR blocked the mitogenic response induced by sPLA2-IIA. This study showed that sPLA2-IIA is able to bring into play EGFR to trigger its signaling and that PKC leads the distribution of resources. Interestingly, we found that this is not a cell-specific response, because sPLA2-IIA was also able to transactivate EGFR in MCF7 human breast cancer cells. Therefore, this mechanism could contribute to worsen the prognosis of a tumor in an inflammatory microenvironment. We also present more links of the tumor chain possibly susceptible to targeting.
Materias Unesco
3201.01 Oncología
ISSN
1522-8517
Revisión por pares
SI
Patrocinador
Ministerio de Ciencia, Innovación y Universidades (grants SAF2005-01242 and SAF2009-08407)
Junta de Castilla y León (grant CSI11A08)
Junta de Castilla y León (grant CSI11A08)
Nota
Anexo: Erratum: Secreted
PLA
2 induces proliferation in astrocytoma through the
EGF receptor: another inflammation-cancer
Version del Editor
Propietario de los Derechos
© 2010 Oxford University Press
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
Aparece en las colecciones
Arquivos deste item
Exceto quando indicado o contrário, a licença deste item é descrito como Attribution-NonCommercial-NoDerivatives 4.0 Internacional