БИОХИМИЯ, 2018, том 83, вып. 12, с. 1802–1811

УДК 616-006.6

Роль эпителиально-мезенхимального перехода в опухолевой прогрессии

Обзор

© 2018 Н.А. Глушанкова *, И.Ю. Житняк, С.Н. Рубцова

Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина Министерства здравоохранения Российской Федерации, 115478 Москва, Россия; электронная почта: natglu@hotmail.com

Поступила в редакцию 01.09.2018
После доработки 17.09.2018

DOI: 10.1134/S0320972518120059

КЛЮЧЕВЫЕ СЛОВА: опухоли, карциномы, неопластическая трансформация, опухолевая прогрессия, эпителиально-мезенхимальный переход, Е-кадхерин.

Аннотация

Эпителиально-мезенхимальный переход (ЭМП) – фундаментальный процесс морфогенеза, в ходе которого эпителиальные клетки приобретают мезенхимальный фенотип. Многочисленные данные свидетельствуют о важнейшей роли ЭМП в опухолевой прогрессии. В карциномах при индукции ЭМП в результате активации онкогенного сигналинга, а также под воздействием гипоксии или факторов опухолевого микроокружения, раковые клетки разрывают контакты с соседними клетками и приобретают способность к миграции и инвазии. Подавление экспрессии белка стабильной межклеточной адгезии, Е-кадхерина, в опухоли считается неблагоприятным прогностическим маркером. Для многих опухолей характерен неполный ЭМП, при котором опухолевые клетки, приобретая мезенхимальные характеристики, сохраняют эпителиальные маркеры, в частности, Е-кадхерин. В клетках с гибридным эпителиально-мезенхимальным фенотипом Е-кадхерин аккумулируется в межклеточных адгезионных контактах, которые, в отличие от межклеточных адгезионных контактов нормальных эпителиоцитов, нестабильны. Межклеточные адгезионные контакты, образованные Е-кадхерином, способствуют эффективной коллективной миграции и инвазии опухолевых клеток, их выживанию на этапах метастазирования. Пластичность гибридного эпителиально-мезенхимального фенотипа повышает адаптационные возможности опухолевых клеток. При вступлении в ЭМП опухолевые клетки приобретают резистентность к химиотерапии и способность подавлять иммунный ответ. Появление опухолевых стволовых клеток при активации программы ЭМП показано для многих типов карцином.

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Финансирование

Работа поддержана грантом РНФ (16-15-10288).

Конфликт интересов

Авторы заявляют, что между ними отсутствует конфликт интересов.

Соблюдение этических норм

Настоящий обзор не содержит описания каких-либо исследований с использованием людей или животных в качестве объектов.

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