Activation of protein kinase p70S6K1 in peripheral blood mononuclear cells of patients with cancer and diabetes

Authors

  • T.S. Vatseba Ivano-Frankivsk National Medical University
  • L.K. Sokolova V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine, Kyiv
  • V.V. Pushkarev V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine, Kyiv
  • O.I. Kovzun V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine, Kyiv
  • V.M. Pushkarev V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine, Kyiv
  • M.D. Tronko V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine, Kyiv

DOI:

https://doi.org/10.15407/dopovidi2019.09.099

Keywords:

cancer, p70S6K1, peripheral mononuclear blood cells, type 2 diabetes

Abstract

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.

Downloads

Download data is not yet available.

References

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

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

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).

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

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

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.

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

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 5AMP-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

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

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).

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

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

Downloads

Published

24.04.2024

How to Cite

Vatseba, T., Sokolova, L., Pushkarev, V., Kovzun, O., Pushkarev, V., & Tronko, M. (2024). Activation of protein kinase p70S6K1 in peripheral blood mononuclear cells of patients with cancer and diabetes . Reports of the National Academy of Sciences of Ukraine, (9), 99–104. https://doi.org/10.15407/dopovidi2019.09.099

Issue

No. 9 (2019): Reports of the National Academy of Sciences of Ukraine

Section

Medicine

License

Copyright (c) 2024 Reports of the National Academy of Sciences of Ukraine

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Most read articles by the same author(s)

1 2 > >>