Роль интегрированного ответа опухолевых клеток на стресс, аутофагии и шаперонов в возникновении рецидивов резистентных опухолей
- Авторы: Зубова С.Г.1, Гнедина О.О.1
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Учреждения:
- Институт цитологии РАН
- Выпуск: Том 65, № 3 (2023)
- Страницы: 246-258
- Раздел: Статьи
- URL: https://journals.rcsi.science/0041-3771/article/view/140084
- DOI: https://doi.org/10.31857/S0041377123030100
- EDN: https://elibrary.ru/VDVTWZ
- ID: 140084
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Аннотация
Химио- и радиотерапия представляют собой для опухолевых клеток колоссальный стрессорный фактор. В ответ на терапию активируется вся эволюционно закрепленная реакция клеток на стресс. Это происходит на всех уровнях организации клетки, а именно на белковом уровне и уровне ДНК. В этот ответ включаются система протеостаза клетки, системы репарации ДНК, гены-онкосупрессоры и многие другие системы клетки. Мы рассмотрим роль в этих процессах основных систем протеостаза, а именно макроаутофагии и шаперонов, которые являются частью интегрированного ответа клетки на стресс. В результате ответа клетки на стресс, опухолевая клетка становится еще менее дифференцированной, активируя необходимые для выживания гены и внутриклеточные системы. Клетки, которые ответили на стресс таким образом, имеют более агрессивный фенотип, который оказывается значительно устойчивее к терапии. Под воздействием стресса клетка эволюционно упрощается, что дает ей дополнительные шансы для выживания. Аутофагия, с одной стороны, способствует снижению дифференцировки опухолевой клетки, ее пластичности, а с другой – поддерживает определенную стабильность, отвечая за целостность генома и освобождая клетку от поврежденных органелл и дефектных белков. И аутофагия, и шапероны способствуют приобретению опухолью множественной лекарственной устойчивости, что еще более затрудняет терапию. Понимание этих процессов с учетом многостадийности канцерогенеза делает возможной разработку новых терапевтических подходов.
Ключевые слова
Об авторах
С. Г. Зубова
Институт цитологии РАН
Автор, ответственный за переписку.
Email: egretta_julia@mail.ru
Россия, Санкт-Петербург
О. О. Гнедина
Институт цитологии РАН
Email: egretta_julia@mail.ru
Россия, Санкт-Петербург
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