Исследование молекулярных механизмов RAL-опосредованной стимуляции метастазирования тема диссертации и автореферата по ВАК РФ 14.00.14, кандидат биологических наук Рыбко, Вера Александровна

• Рыбко, Вера Александровна
• кандидат биологических наук
• 2009

Заключение диссертации по теме «Онкология», Рыбко, Вера Александровна

Выводы

1. Получены линии, стабильно экспрессирующие различные формы белков RalA и RalB: активные ГТФ-связанные белки, а также эффекторные мутанты, неспособные взаимодействовать с PLD, RalBPl или с комплексом экзоциста.

2. Активность белков Ral (в большей степени RalB) приводит к стимуляции спонтанной метастатической активности клеток Het-SR. Мутация, блокирующия взаимодействие с PLD, отменяет RalB-опосредованную стимуляцию метастазирования.

3. Белки Ral стимулируют пролиферацию, подвижность и рост в условиях разреженной популяции исследованных клеток.

4. Активная форма RalB в большей степени, чем RalA активирует инвазию in vitro, что коррелирует со стимуляцией миграции клеток по градиенту ростовых факторов. При этом для стимуляции инвазии как RalB, так и RalA необходимо взаимодействие с RalBPl.

5. Различные мутантые формы белков Ral влияют на активность белков, ремоделирующих ВКМ (ММР1 и ММР9). RalA, в отличие от RalB, усиливает активность протеазы иРА, что опосредовано взаимодействием с RalBPl и комплексом экзоциста.

6. Активные формы RalA и RalB, а также их эффекторные мутанты по-разному модулируют внутриклеточную передачу сигнала и экспрессию белков, потенциально ассоциированных с метастазированием: фосфорилирование киназы JNK1, экспессию CyclinDl, Cav-1 и CD24.

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