Cell and Tissue BiologyCell and Tissue BiologyЦитология0041-37713034-6061The Russian Academy of Sciences66964510.31857/S0041377123030100VDVTWZArticlesСтатьиThe Role of the Integrated Response of Tumor Cells to Stress, Autophagy, and Chaperones in the Origin of Recurrent Resistant TumorsРоль интегрированного ответа опухолевых клеток на стресс, аутофагии и шаперонов в возникновении рецидивов резистентных опухолейZubovaS. G.ЗубоваС. Г.egretta_julia@mail.ruGnedinaO. O.ГнединаО. О.egretta_julia@mail.ruInstitute of Cytology of the Russian Academy of SciencesИнститут цитологии РАН0105202365324625827022025Copyright ©; 2023, С.Г. Зубова, О.О. ГнединаCopyright ©; 2023, С.Г. Зубова, О.О. Гнедина2023С.Г. Зубова, О.О. ГнединаС.Г. Зубова, О.О. Гнединаhttps://vietnamjournal.ru/0041-3771/article/view/669645

Chemotherapy and radiotherapy are a colossal stress factor for tumor cells. In response to therapy, the entire evolutionarily fixed response of cells to stress is activated. This happens at all levels of cell organization, namely at the protein level and the DNA level. This response involves the cell proteostasis system, DNA repair systems, tumor suppressor genes, and many other cell systems. We will consider the role of the main systems of proteostasis in these processes, namely, macroautophagy and chaperones, which are part of the integrated response of the cell to stress. As a result of the cell’s response to stress, the tumor cell becomes even less differentiated, activating the genes and intracellular systems necessary for survival. Cells that have responded to stress in this way have a more aggressive phenotype that is significantly more resistant to therapy. Under the influence of stress, the cell evolutionarily simplifies, which gives it additional chances for survival. On the one hand, autophagy contributes to a decrease in tumor cell differentiation and its plasticity, and on the other hand, it maintains a certain stability, being responsible for the integrity of the genome and freeing the cell from damaged organelles and defective proteins. Both autophagy and chaperones contribute to the acquisition of multidrug resistance by the tumor, which further complicates therapy. Understanding these processes makes it possible to develop new therapeutic approaches, taking into account the multistage nature of carcinogenesis.

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.

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