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La disociación de las vías de señalización de EphB2 que median la proliferación de células progenitoras y la
Maria Genander1, Michael M Halford, Nan-Jie Xu
1Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Cell
|November 17, 2009
Resumen
La señalización del receptor EphB2 en el intestino tiene una doble función. Su función independiente de la quinasa controla el posicionamiento celular, mientras que su actividad quinasa regula la proliferación, ofreciendo una estrategia para atacar el crecimiento del adenoma.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Oncología Oncología.
Sus antecedentes:
- Los protooncogenes generalmente impulsan la proliferación celular, pero los receptores EphB son una excepción.
- Los receptores EphB promueven la proliferación de células intestinales y actúan como supresores de tumores al regular la migración celular e inhibir el crecimiento invasivo.
Objetivo del estudio:
- Investigar las funciones independientes del receptor EphB2 en el control de la migración y la proliferación celular.
- Para dilucidar las vías moleculares involucradas en la señalización mediada por EphB2 en el epitelio intestinal.
Principales métodos:
- Investigó las vías de señalización de EphB2 en las células epiteliales intestinales.
- Utilizó técnicas de biología molecular y celular para diseccionar la señalización dependiente y independiente de la quinasa.
- Se analizaron cambios en la señalización de EphB2 durante la progresión del adenoma de colon humano a carcinoma.
Principales resultados:
- El receptor EphB2 controla el posicionamiento celular a través de una vía independiente de la quinasa que involucra a la fosfatidilinositol 3-cinasa.
- La actividad de la tirosina quinasa EphB2 regula la proliferación celular a través de una vía de la Abl-ciclina D1.
- La regulación de la ciclina D1 se disocia de la señalización de EphB en el carcinoma de colon humano, lo que permite la proliferación continua y el crecimiento invasivo.
Conclusiones:
- Las vías de señalización EphB2 que controlan la migración celular y la proliferación están reguladas de forma independiente.
- La disociación de estas vías durante la progresión del cáncer de colon ofrece un objetivo terapéutico.
- La inhibición selectiva del efecto mitogénico de EphB2, sin comprometer su función supresora de tumores, presenta una estrategia farmacológica para la supresión del crecimiento del adenoma.
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