Effect of PI3K/Akt Signaling Pathway on PRAS40Thr246 Phosphorylation in Gastric Cancer Cells
Abstract
Background: We aimed to investigate the effect of PI3K/Akt signaling pathway on PRAS40Thr246 phosphorylation in gastric cancer cells.
Methods: The study was conducted from April 2017 to January 2018 in Zhongshan Hospital, Xiamen University, Xiamen, China. Gastric cancer cells were divided into three groups: gastric cancer cell group, LY294002 group and MK-2206 group. Specific tests were conducted accordingly.
Results: Inhibition of PI3K/Akt signaling pathway activation and PRAS40Thr246 phosphorylation could inhibit proliferation and invasion and promote apoptosis of gastric cancer cells, and PRAS40Thr246 phosphorylation could activate PI3K/Akt signaling pathway.
Conclusion: The levels of PI3K/Akt signaling pathway related proteins and p-PRAS40Thr246 were significantly increased in gastric cancer cells. p-PRAS40-Thr246 was able to reflect the activation of the PI3K/Akt signaling pathway, reflecting the sensitivity of the PI3K/AKT signaling pathway to inhibitors.
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4. Sano T, Coit DG, Kim HH, Roviello F, Kassab P, Wittekind C, Yamamoto Y, Ohashi Y (2018). Proposal of a new stage grouping of gastric cancer for TNM clas-sification: International Gastric Cancer Association staging project. Gastric Cancer, 20: 217-225.
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7. Hao NB, Tang B, Wang GZ, et al (2015). Hepatocyte growth factor (HGF) upregu-lates heparanase expression via the PI3K/Akt/NF-kappaB signaling pathway for gastric cancer metastasis. Cancer Lett, 361: 57-66.
8. Riquelme I, Tapia O, Leal P, et al (2016). miR-101-2, miR-125b-2 and miR-451a act as potential tumor suppressors in gas-tric cancer through regulation of the PI3K/AKT/mTOR pathway. Cell Oncol (Dordr), 39: 23-33.
9. Andersen JN, Sathyanarayanan S, Di Bacco A, et al (2010). Pathway-based identifica-tion of biomarkers for targeted therapeu-tics: personalized oncology with PI3K pathway inhibitors. Sci Transl Med, 2: 43ra55.
10. Lu YZ, Deng AM, Li LH, Liu GY, Wu GY (2014). Prognostic role of phospho-PRAS40 (Thr246) expression in gastric cancer. Arch Med Sci, 10: 149-153.
11. Katai H, Mizusawa J, Katayama H, et al (2017). Short-term surgical outcomes from a phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer: Japan Clinical On-cology Group Study JCOG0912. Gastric Cancer, 20: 699-708.
12. Porta C, Paglino C, Mosca A (2014). Target-ing PI3K/Akt/mTOR Signaling in Can-cer. Front Oncol, 4: 64.
13. Polivka J, Jr., Janku F (2014). Molecular tar-gets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther, 142: 164-175.
14. Hao W, Yuan X, Yu L, Gao C, Sun X, Wang D, Zheng Q (2015). Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT sig-naling pathways. Sci Rep, 5: 10336.
15. Tapia O, Riquelme I, Leal P, et al (2014). The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance. Virchows Arch, 465: 25-33.
16. Yuan K, Wu H, Wang Y, Chen H, Jiao M, Fu R (2015). Phospho-PRAS40(Thr246) predicts trastuzumab response in patients with HER2-positive metastatic breast cancer. Oncol Lett, 9: 785-789.
17. Hao J, Li F, Liu W, Liu Q, Liu S, Li H, Duan H (2014). Phosphorylation of PRAS40-Thr246 involved in renal lipid accumula-tion of diabetes. J Cell Physiol, 229: 1069-1077.
18. Swierczynski J, Hebanowska A, Sledzinski T (2014). Role of abnormal lipid metabo-lism in development, progression, diag-nosis and therapy of pancreatic cancer. World J Gastroenterol, 20: 2279-2303.
19. Cui M, Wang Y, Sun B, Xiao Z, Ye L, Zhang X (2014). MiR-205 modulates ab-normal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA. Biochem Biophys Res Commun, 444: 270-275.
20. Imai Y, Yamagishi H, Ono Y, Ueda Y (2012). Versatile inhibitory effects of the flavonoid-derived PI3K/Akt inhibitor, LY294002, on ATP-binding cassette transporters that characterize stem cells. Clin Transl Med, 1: 24.
21. Wang SQ, Wang C, Chang LM, et al (2016). Geridonin and paclitaxel act synergistical-ly to inhibit the proliferation of gastric cancer cells through ROS-mediated regu-lation of the PTEN/PI3K/Akt pathway. Oncotarget, 7: 72990-73002.
2. van der Post RS, van Dieren J, Grelack A, et al (2018). Outcomes of screening gas-troscopy in first-degree relatives of pa-tients fulfilling hereditary diffuse gastric cancer criteria. Gastrointest Endosc, 87: 397-404.e392.
3. Kim JW, Nam KH, Ahn SH, et al (2018). Prognostic implications of immunosup-pressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric can-cer. Gastric Cancer, 19: 42-52.
4. Sano T, Coit DG, Kim HH, Roviello F, Kassab P, Wittekind C, Yamamoto Y, Ohashi Y (2018). Proposal of a new stage grouping of gastric cancer for TNM clas-sification: International Gastric Cancer Association staging project. Gastric Cancer, 20: 217-225.
5. Sinha D, Kalimutho M, Bowles J, et al (2018). Cep55 overexpression causes male-specific sterility in mice by suppress-ing Foxo1 nuclear retention through sus-tained activation of PI3K/Akt signaling. Faseb J, 32: 4984-4999.
6. Mayer IA, Arteaga CL (2016). The PI3K/AKT Pathway as a Target for Can-cer Treatment. Annu Rev Med, 67: 11-28.
7. Hao NB, Tang B, Wang GZ, et al (2015). Hepatocyte growth factor (HGF) upregu-lates heparanase expression via the PI3K/Akt/NF-kappaB signaling pathway for gastric cancer metastasis. Cancer Lett, 361: 57-66.
8. Riquelme I, Tapia O, Leal P, et al (2016). miR-101-2, miR-125b-2 and miR-451a act as potential tumor suppressors in gas-tric cancer through regulation of the PI3K/AKT/mTOR pathway. Cell Oncol (Dordr), 39: 23-33.
9. Andersen JN, Sathyanarayanan S, Di Bacco A, et al (2010). Pathway-based identifica-tion of biomarkers for targeted therapeu-tics: personalized oncology with PI3K pathway inhibitors. Sci Transl Med, 2: 43ra55.
10. Lu YZ, Deng AM, Li LH, Liu GY, Wu GY (2014). Prognostic role of phospho-PRAS40 (Thr246) expression in gastric cancer. Arch Med Sci, 10: 149-153.
11. Katai H, Mizusawa J, Katayama H, et al (2017). Short-term surgical outcomes from a phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer: Japan Clinical On-cology Group Study JCOG0912. Gastric Cancer, 20: 699-708.
12. Porta C, Paglino C, Mosca A (2014). Target-ing PI3K/Akt/mTOR Signaling in Can-cer. Front Oncol, 4: 64.
13. Polivka J, Jr., Janku F (2014). Molecular tar-gets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther, 142: 164-175.
14. Hao W, Yuan X, Yu L, Gao C, Sun X, Wang D, Zheng Q (2015). Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT sig-naling pathways. Sci Rep, 5: 10336.
15. Tapia O, Riquelme I, Leal P, et al (2014). The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance. Virchows Arch, 465: 25-33.
16. Yuan K, Wu H, Wang Y, Chen H, Jiao M, Fu R (2015). Phospho-PRAS40(Thr246) predicts trastuzumab response in patients with HER2-positive metastatic breast cancer. Oncol Lett, 9: 785-789.
17. Hao J, Li F, Liu W, Liu Q, Liu S, Li H, Duan H (2014). Phosphorylation of PRAS40-Thr246 involved in renal lipid accumula-tion of diabetes. J Cell Physiol, 229: 1069-1077.
18. Swierczynski J, Hebanowska A, Sledzinski T (2014). Role of abnormal lipid metabo-lism in development, progression, diag-nosis and therapy of pancreatic cancer. World J Gastroenterol, 20: 2279-2303.
19. Cui M, Wang Y, Sun B, Xiao Z, Ye L, Zhang X (2014). MiR-205 modulates ab-normal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA. Biochem Biophys Res Commun, 444: 270-275.
20. Imai Y, Yamagishi H, Ono Y, Ueda Y (2012). Versatile inhibitory effects of the flavonoid-derived PI3K/Akt inhibitor, LY294002, on ATP-binding cassette transporters that characterize stem cells. Clin Transl Med, 1: 24.
21. Wang SQ, Wang C, Chang LM, et al (2016). Geridonin and paclitaxel act synergistical-ly to inhibit the proliferation of gastric cancer cells through ROS-mediated regu-lation of the PTEN/PI3K/Akt pathway. Oncotarget, 7: 72990-73002.
| Files | ||
| Issue | Vol 48 No 12 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i12.3551 | |
| Keywords | ||
| Gastric cancer; LY294002 MK-2206 Phosphorylation PI3K/Akt signaling pathway PRAS40-Thr246 | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
LU Y, LI L, WU G, ZHUO H, LIU G, CAI J. Effect of PI3K/Akt Signaling Pathway on PRAS40Thr246 Phosphorylation in Gastric Cancer Cells. Iran J Public Health. 2019;48(12):2196-2204.
