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

2020 ◽  
Vol 15 (3) ◽  
pp. 110-117
Author(s):  
Liudmila V. Spirina ◽  
Sventlana Yu. Chizhevskaya ◽  
Irina V. Kondakova ◽  
Nataliya V. Tarasenko

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.

Author(s):  
Liudmila Spirina ◽  
Svetlana Chizhevskaya ◽  
Irina Kondakova ◽  
Natalia Tarasenko

Autophagy is an important intracellular process that ensures cell death and survival. Activation of molecular mechanisms in thyroid cancer development is associated with a change in the AKT/m-TOR 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 molecular mechanisms of the autophagy development, its association with key signaling cascades, in particular AKT/m-TOR signaling pathway. A significant signaling molecule m-TOR, in this case, contributes to the development of the tumor, the proliferation of transformed cells, apoptosis inhibition, and to the development of autophagy. The significance of this phenomenon at all stages of carcinogenesis, affecting 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 RET1 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.


2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Bu-gao Zhou ◽  
Hai-mei Zhao ◽  
Xiu-yun Lu ◽  
Xin Wang ◽  
Yong Zou ◽  
...  

The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression. However, the secretion of albumin, liver weight, and index of liver weight were elevated. Microscopic examination showed that EZP restored pathological liver injury. Meanwhile, Rheb and mammalian target of rapamycin (mTOR) activation were suppressed, and tuberous sclerosis complex (TSC) expression was elevated in liver tissues induced by 2-AAF/PHx and accompanied with lower-expression of Bax, Notch1, p70S6K, and 4E-EIF and upregulated levels of Bcl-2 and Cyclin D. Hepatoprotective effect of EZP was possibly realized via inhibiting TSC/mTOR signaling pathway to suppress excessive apoptosis of hepatocyte.


2015 ◽  
Vol 468 (1-2) ◽  
pp. 394-399 ◽  
Author(s):  
Yue Zhou ◽  
Xin He ◽  
Yili Chen ◽  
Yiyi Huang ◽  
Lingling Wu ◽  
...  

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