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

L. Spirina, S. Chizhevskaya, I. Kondakova, N. Tarasenko
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引用次数: 3

Abstract

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 BRAF 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.
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自噬在甲状腺肿瘤发生发展中的作用,与AKT/m-TOR信号通路激活有关
自噬是支持细胞死亡和存活的重要细胞内过程。肿瘤的发生与AKT/mTOR信号通路状态的改变有关。同时,保护性自噬的存在已被证实是疾病进展和治疗耐药形成的机制之一。本文综述了自噬发生的重要机制及其与AKT/mTOR信号通路的关系。TORC1复合体中的一个分子mTOR与肿瘤发生有关,它提供转化细胞的增殖、细胞凋亡抑制和自噬的发展。注意到这种现象在癌变的所有阶段都有参与,影响了主要的信号激酶:AKT, mTOR。研究表明,在大多数情况下,这种机制是导致疾病进展和对治疗产生耐药性的原因。甲状腺癌的发展与BRAF突变、RET癌蛋白的激活以及该疾病的放射抵抗形式的形成有关,这与自噬的分子特性有关。鉴于这种现象对肿瘤发生过程的影响不一致,其在甲状腺癌发展中的作用仍然未知。
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