| Title | Phosphorylation of PRAS40 in leukocytes 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. |
| DOI | 10.15407/dopovidi2019.05.102 |
| Issue | 5 |
| Section | Medicine |
| Pagination | 102-107 |
| Date Published | 05/2019 |
| Language | Ukrainian |
| Abstract | We have studied the activity of mTORC1 (mammalian target of rapamycin complex 1) in leukocytes of patients with cancer and diabetes by immuno-enzyme analysis. It has been shown that, in the leukocytes of patients with cancer and type 2 diabetes, the phosphorylation of the mTORC1 inhibitor — PRAS40 (proline-rich substrate 40kDa) increases, which indicates the activation of kinase, which plays an important role in the formation of the insulin resistance and tumor progression. However, in patients with cancer and diabetes, the phosphorylation of PRAS40 and, accordingly, the activity of mTORC1 are significantly reduced as compared with the control. The mechanisms of mTORC1 activation and its significance for cancer and diabetes are discussed. |
| Keywords | cancer, mTORC1, PRAS40, type 2 diabetes |
1. Yang, J., Nishihara, R., Zhang, X. et al. (2017). Energy sensing pathways: Bridging type 2 diabetes and colorectal cancer? J. Diabetes Complications., 31, No. 7, pp. 1228-1236. doi: https://doi.org/10.1016/j.jdiacomp.2017.04.012
2. Wang, H., Zhang, Q., Wen, Q. et al. (2012). Proline-rich Akt substrate of 40kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway. Cell Signal., 24, No. 1, pp. 17-24. doi: https://doi.org/10.1016/j.cellsig.2011.08.010
3. Andersen, J. N., Sathyanarayanan, S., Di Bacco, A. et al. (2010). Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors. Sci. Transl. Med., 2, No. 43, 43ra55. doi: https://doi.org/10.1126/scitranslmed.3001065
4. Wiza, C., Chadt, A., Blumensatt, M. et al. (2014). Over-expression of PRAS40 enhances insulin sensitivity in skeletal muscle. Arch. Physiol. Biochem., 120, No. 2, pp. 64-72. doi: https://doi.org/10.3109/13813455.2014.894076
5. Oshiro, N., Takahashi, R., Yoshino, K. et al. (2007). The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1. J. Biol. Chem., 282, No. 28, pp. 20329-20339. doi: https://doi.org/10.1074/jbc.M702636200
6. Havel, J. J., Li, Z., Cheng, D., Peng, J. & Fu, H. (2014). Nuclear PRAS40 couples the Akt/mTORC1 signaling axis to the RPL11-HDM2-p53 nucleolar stress response pathway. Oncogene. doi: https://doi.org/10.1038/onc.2014.91
7. Wiza, C., Nascimento, E. B. M. & Ouwens, M. D. (2015). AKT1S1 (AKT1 substrate 1 (proline-rich)). Atlas Genet. Cytogenet. Oncol. Haematol., 19, No. 12, pp. 679-683.
8. Hong-Brown, L. Q., Brown, C. R., Kazi, A. A. et al. (2010). Alcohol and PRAS40 knockdown decrease mTOR activity and protein synthesis via AMPK signaling and changes in mTORC1 interaction. J. Cell. Biochem., 109, No. 6, pp. 1172-1184. doi: https://doi.org/10.1002/jcb.22496
9. Dituri, F., Mazzocca, A., Giannelli, G. & Antonaci, S. (2011). PI3K functions in cancer progression, anticancer immunity and immune evasion by tumors. Clin. Dev. Immunol., 947858. doi: https://doi.org/10.1155/2011/947858
10. De Oliveira, C. E., Oda, J. M., Losi Guembarovski, R. et al. (2014). CC chemokine receptor 5: the interface of host immunity and cancer. Dis. Markers., 126954. doi: https://doi.org/10.1155/2014/126954
11. 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).
12. 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
13. Jiang, N., Hjorth-Jensen, K., Hekmat, O. et al. (2015). In vivo quantitative phosphoproteomic profiling identifies novel regulators of castration-resistant prostate cancer growth. Oncogene, 34, No. 32, pp. 2764-2776. doi: https://doi.org/10.1038/onc.2014.206
14. 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
15. Pushkarev, V. M., Sokolova, L. K., Pushkarev, V. V. & Tronko, M. D. (2018). Biochemical mechanisms connecting diabetes and cancer. Effects of metformin. Endokrynologia, 23, No. 2, pp. 167-179 (in Russian).
