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Роль аутофагии в развитии опухолей щитовидной железы, связь с активацией AKT/m-TOR сигнального пути

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Аутофагия является важным внутриклеточным процессом, обеспечивающим гибель и выживаемость клеток. Молекулярные механизмы развития злокачественных новообразований связаны с изменением состояния AKT/mTOR сигнального пути. При этом доказано существование защитной аутофагии как одного из механизмов прогрессирования заболевания и формирования резистентности к лечению. В обзоре описаны молекулярные механизмы развития аутофагии, ее ассоциации с ключевыми сигнальными каскадами, в частности AKT/mTOR. Значимая сигнальная молекула mTOR в составе комплекса TORC1 в этом случае не только способствует развитию опухоли, пролиферации трансформированных клеток, их уходу от апоптоза, но и развитию аутофагии. Отмечено значение данного явления на всех этапах онкогенеза, влияющего на протеинкиназы AKT, mTOR. Показано, что в подавляющем большинстве случаев этот механизм срабатывает при прогрессировании заболевания и развитии резистентности к лечению. Развитие рака щитовидной железы, сопряженное с мутацией гена i>BRAF/i> и активацией онкобелка RET, а также ответ на лечение и формирование радиойодрезистентных форм заболевания определяются молекулярными особенностями регуляции аутофагии. Учитывая противоречивость данных относительно влияния аутофагии на процессы онкогенеза, до сих пор остается неизвестной ее роль в патогенезе злокачественных опухолей данной локализации.

Ключевые слова:
рак щитовидной железы, аутофагия, AKT/mTOR сигнальный каскад, BRAF, RET, thyroid cancer, autophagy, AKT/mTOR signaling pathway, BRAF, RET

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The role of autophagy in the thyroid tumors development, connection with the AKT/m-TOR signaling pathway activation

Autophagy is an important intracellular process that supports cell death and survival. Oncogenesis is associated with a change in the AKT/mTOR signaling pathway status. At the same time, the existence of protective autophagy, as one of the mechanisms of disease progression and the formation of resistance to treatment, has been proven. The review describes the significant mechanisms of the autophagy development, its association with AKT/mTOR signaling pathway. A molecule mTOR in TORC1 complex is associated with the oncogenesis, it provides the proliferation of transformed cells, apoptosis inhibition, and to the development of autophagy. The participation of this phenomenon at all stages of carcinogenesis, influencing on the main signal kinases: AKT, mTOR, is noted. It is shown that in most cases this mechanism is responsible for the progression of the disease and the development of resistance to treatment. The development of thyroid cancer associated with the i>BRAF/i> mutation and with the activation of the RET oncoprotein, as well as with the formation of radio-resistant forms of the disease is associated with molecular peculiarities of autophagy. Given the inconsistency of this phenomenon regarding their influence on the processes of oncogenesis, its role in the development of thyroid cancer is still unknown.

Keywords:
рак щитовидной железы, аутофагия, AKT/mTOR сигнальный каскад, BRAF, RET, thyroid cancer, autophagy, AKT/mTOR signaling pathway, BRAF, RET