|Title||Activation of protein kinase p70S6K1 in peripheral blood mononuclear cells of patients with cancer and diabetes|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Vatseba, TS, Sokolova, LK, Pushkarev, VV, Kovzun, OI, Pushkarev, VM, Tronko, MD|
|Abbreviated Key Title||Dopov. Nac. akad. nauk Ukr.|
The IRS/PI3K/Akt/mTOR/p70S6K signaling cascade controls the cell growth and homeostasis in response to environmental signals such as levels of amino acids, glucose, energy, oxygen, and action of growth factors. The final link of this cascade is protein kinase p70S6K, which controls the protein synthesis, ribosomal biogenesis, cell cycle, apoptosis, splicing of mRNA, and other important processes. Disturbance of the IRS/PI3K/Akt/mTOR/ p70S6K cascade regulation can lead to serious diseases such as cancer, obesity and type 2 diabetes with complications. We study the activation of p70S6K1 in peripheral mononuclear blood cells (PMBC) of patients with cancer and diabetes by immunoenzyme analysis. It has been shown that, in PMBC patients with cancer and diabetes, the phosphorylation of p70S6K1 (Thr389) increases, indicating the activation of a kinase, which plays an important role in the formation of insulin resistance and tumor progression. Perhaps, this is due to elevated levels of insulin and IGF-1 in blood of these groups. However, in cancer patients with diabetes, the phosphorylation of p70S6K1 and, accordingly, its activity are significantly reduced compared with groups of patients with cancer or diabetes. The mechanisms for such a decrease in p70S6K1 activation are discussed.
|Keywords||cancer, p70S6K1, peripheral mononuclear blood cells, type 2 diabetes|
1. Yang, J., Nishihara, R., Zhang, X., Ogino, S. & Qian, Z. R. (2017). Energy sensing pathways: Bridging type 2 diabetes and colorectal cancer? J. Diabetes Complicat., 31, No. 7, pp. 1228-1236. doi: https://doi.org/10.1016/j.jdiacomp.2017.04.012
2. Hong, S., Zhao, B., Lombard, D. B., Fingar, D. C. & Inoki, K. (2014). Cross-talk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation. J. Biol. Chem., 289, No. 19, pp. 13132-13141. doi: https://doi.org/10.1074/jbc.M113.520734
3. Tronko, N. D., Pushkarev, V. M., Sokolova, L. K., Pushkarev, V. V. & Kovzun, O. I. (2018). Molecular mechanisms of pathogenesis of diabetes and its complications. Kyiv: Medkniga (in Russian).
4. Tavares, M. R., Pavan, I. C., Amaral, C. L., Meneguello, L., Luchessi, A. D. & Simabuco, F. M. (2015). The S6K protein family in health and disease. Life Sci., 131, pp. 1-10. doi: https://doi.org/10.1016/j.lfs.2015.03.001
5. de Oliveira, C. E., Oda, J. M., Losi Guembarovski, R., de Oliveira, K. B., Ariza, C. B., Neto, J. S., Banin Hirata, B. K. & Watanabe, M. A. (2014). CC chemokine receptor 5: the interface of host immunity and cancer. Dis. Markers., 2014, 126954. doi: https://doi.org/10.1155/2014/126954
6. Sokolova, L. K., Pushkarev, V. M., Pushkarev, V. V. & Tronko, N. D. (2017). Diabetes and atherosclerosis. Cellular mechanisms of pathogenesis. Endokrinologia, 22, No. 2, pp. 127-138.
7. Dituri, F., Mazzocca, A., Giannelli, G. & Antonaci, S. (2011). PI3K functions in cancer progression, anticancer immunity and immune evasion by tumors. Clin. Dev. Immunol., 2011, 947858. doi: https://doi.org/10.1155/2011/947858
8. Sokolova, L. K., Pushkarev, V. M., Belchina, Y. B., Pushkarev, V. V. & Tronko, N. D. (2018). Effect of combined treatment with insulin and metformin on 5AMP-activated protein kinase activity in lymphocytes of diabetic patients. Dopov. Nac. akad. nauk Ukr., No. 5, pp. 100-104. doi: https://doi.org/10.15407/dopovidi2018.05.100
9. Kim, L. C., Cook, R. S. & Chen J. (2017). mTORC1 and mTORC2 in cancer and the tumor microenvironment. Oncogene, 36, No. 16, pp. 2191-2201. doi: https://doi.org/10.1038/onc.2016.363
10. Pushkarev, V. M., Sokolova, L. K., Pushkarev, V. V. & Tronko, M. D. (2016). The role of AMPK and mTOR in the development of insulin resistance and type 2 diabetes. The mechanism of metformin action (literature review). Probl. Endocrin. Pathol., No. 3, pp. 77-90 (in Russian).
11. Vatseba, T. S., Sokolova, L. K., Pushkarev, V. V., Kovzun, O. I., Pushkarev, V. M. & Tronko, M. D. (2019). Expression of protein kinase p70S6K in leukocytes of patients with cancer and diabetes. Endokrinologia, 24, No. 1, pp. 26-30. doi: https://doi.org/10.31793/1680-1466.2019.24-1.5
12. Bahrami, B. F., Ataie-Kachoie, P., Pourgholami, M. H. & Morris, D. L. (2014). p70 Ribosomal protein S6 kinase (Rps6kb1): an update. J. Clin. Pathol., 67, No. 12, pp. 1019-1025. doi: https://doi.org/10.1136/jclinpath-2014-202560