Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
권호 표지
DOI QR코드

DOI QR Code

EID3 Promotes Glioma Cell Proliferation and Survival by Inactivating AMPKα1

  • Xiang, Yaoxian (Department of Hand Surgery, Huashan Hospital, Fudan University) ;
  • Zhu, Lei (Department of Radiology, Beijing Electric Power Hospital) ;
  • He, Zijian (Department of Neurosurgery, Minhang Hospital, Fudan University) ;
  • Xu, Lei (Department of Hand Surgery, Huashan Hospital, Fudan University) ;
  • Mao, Yuhang (Department of Neurosurgery, Minhang Hospital, Fudan University) ;
  • Jiang, Junjian (Department of Hand Surgery, Huashan Hospital, Fudan University) ;
  • Xu, Jianguang (Department of Hand Surgery, Huashan Hospital, Fudan University)
  • Received : 2021.12.07
  • Accepted : 2022.02.26
  • Published : 2022.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

Objective : EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. Methods : A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. Results : EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. Conclusion : Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.

Keywords

Acknowledgement

This study was supported by Shanghai Municipal Key Clinical specialty (shslczdzk05601).

References

  1. Almiron Bonnin DA, Havrda MC, Israel MA : Glioma cell secretion: a driver of tumor progression and a potential therapeutic target. Cancer Res 78 : 6031-6039, 2018 https://doi.org/10.1158/0008-5472.CAN-18-0345
  2. Barthel FP, Wesseling P, Verhaak RGW : Reconstructing the molecular life history of gliomas. Acta Neuropathol 135 : 649-670, 2018 https://doi.org/10.1007/s00401-018-1842-y
  3. Bavner A, Matthews J, Sanyal S, Gustafsson JA, Treuter E : EID3 is a novel EID family member and an inhibitor of CBP-dependent co-activation. Nucleic Acids Res 33 : 3561-3569, 2005 https://doi.org/10.1093/nar/gki667
  4. Bilanges B, Alliouachene S, Pearce W, Morelli D, Szabadkai G, Chung YL, et al. : Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming of mitochondrial metabolism. Nat Commun 8 : 1804, 2017 https://doi.org/10.1038/s41467-017-01969-4
  5. Boussiotis VA, Charest A : Immunotherapies for malignant glioma. Oncogene 37 : 1121-1141, 2018 https://doi.org/10.1038/s41388-017-0024-z
  6. Cai S, Li Y, Bai JY, Zhang ZQ, Wang Y, Qiao YB, et al. : Gαi3 nuclear translocation causes irradiation resistance in human glioma cells. Oncotarget 8 : 35061-35068, 2017 https://doi.org/10.18632/oncotarget.17043
  7. Carling D : AMPK signalling in health and disease. Curr Opin Cell Biol 45 : 31-37, 2017 https://doi.org/10.1016/j.ceb.2017.01.005
  8. Carroll B, Dunlop EA : The lysosome: a crucial hub for AMPK and mTORC1 signalling. Biochem J 474 : 1453-1466, 2017 https://doi.org/10.1042/BCJ20160780
  9. Chou CC, Lee KH, Lai IL, Wang D, Mo X, Kulp SK, et al. : AMPK reverses the mesenchymal phenotype of cancer cells by targeting the AktMDM2-Foxo3a signaling axis. Cancer Res 74 : 4783-4795, 2014
  10. Cork GK, Thompson J, Slawson C : Real talk: the inter-play between the mTOR, AMPK, and hexosamine biosynthetic pathways in cell signaling. Front Endocrinol (Lausanne) 9 : 522, 2018 https://doi.org/10.3389/fendo.2018.00522
  11. Cui Y, Zhao J, Yi L, Jiang Y : microRNA-153 targets mTORC2 component rictor to inhibit glioma cells. PLoS One 11 : e0156915, 2016 https://doi.org/10.1371/journal.pone.0156915
  12. Dunlop EA, Tee AR : The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient homoeostasis. Biochem Soc Trans 41 : 939- 943, 2013 https://doi.org/10.1042/BST20130030
  13. Fu L, Zhang S, Zhang L, Tong X, Zhang J, Zhang Y, et al. : Systems biology network-based discovery of a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. Oncotarget 6 : 8071-8088, 2015 https://doi.org/10.18632/oncotarget.3513
  14. Ghinda DC, Wu JS, Duncan NW, Northoff G : How much is enough-can resting state fMRI provide a demarcation for neurosurgical resection in glioma? Neurosci Biobehav Rev 84 : 245-261, 2018 https://doi.org/10.1016/j.neubiorev.2017.11.019
  15. Guerineau M, Kriz Z, Kozakova L, Bednarova K, Janos P, Palecek J : Analysis of the Nse3/MAGE-binding domain of the Nse4/EID family proteins. PLoS One 7 : e35813, 2012 https://doi.org/10.1371/journal.pone.0035813
  16. He L, Zhou X, Huang N, Li H, Tian J, Li T, et al. : AMPK regulation of glucose, lipid and protein metabolism: mechanisms and nutritional significance. Curr Protein Pept Sci 18 : 562-570, 2017 https://doi.org/10.2174/1389203717666160627071125
  17. He S, Hu B, Li C, Lin P, Tang WG, Sun YF, et al. : PDXliver: a database of liver cancer patient derived xenograft mouse models. BMC Cancer 18 : 550, 2018 https://doi.org/10.1186/s12885-018-4459-6
  18. Hombach-Klonisch S, Mehrpour M, Shojaei S, Harlos C, Pitz M, Hamai A, et al. : Glioblastoma and chemoresistance to alkylating agents: involvement of apoptosis, autophagy, and unfolded protein response. Pharmacol Ther 184 : 13-41, 2018 https://doi.org/10.1016/j.pharmthera.2017.10.017
  19. Hsieh FS, Chen YL, Hung MH, Chu PY, Tsai MH, Chen LJ, et al. : Palbociclib induces activation of AMPK and inhibits hepatocellular carcinoma in a CDK4/6-independent manner. Mol Oncol 11 : 1035-1049, 2017 https://doi.org/10.1002/1878-0261.12072
  20. Jeon SM : Regulation and function of AMPK in physiology and diseases. Exp Mol Med 48 : e245, 2016 https://doi.org/10.1038/emm.2016.81
  21. Jiang H, Liu W, Zhan SK, Pan YX, Bian LG, Sun B, et al. : GSK621 targets glioma cells via activating AMP-activated protein kinase signalings. PLoS One 11 : e0161017, 2016 https://doi.org/10.1371/journal.pone.0161017
  22. Kim J, Kundu M, Viollet B, Guan KL : AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13 : 132-141, 2011 https://doi.org/10.1038/ncb2152
  23. Konagaya Y, Terai K, Hirao Y, Takakura K, Imajo M, Kamioka Y, et al. : A highly sensitive FRET biosensor for AMPK exhibits heterogeneous AMPK responses among cells and organs. Cell Rep 21 : 2628-2638, 2017 https://doi.org/10.1016/j.celrep.2017.10.113
  24. Lapointe S, Perry A, Butowski NA : Primary brain tumours in adults. Lancet 392 : 432-446, 2018 https://doi.org/10.1016/S0140-6736(18)30990-5
  25. Liu X, Hu X, Kuang Y, Yan P, Li L, Li C, et al. : BCLB, methylated in hepatocellular carcinoma, is a starvation stress sensor that induces apoptosis and autophagy through the AMPK-mTOR signaling cascade. Cancer Lett 395 : 63-71, 2017 https://doi.org/10.1016/j.canlet.2017.02.030
  26. Miller JJ, Shih HA, Andronesi OC, Cahill DP : Isocitrate dehydrogenasemutant glioma: evolving clinical and therapeutic implications. Cancer 123 : 4535-4546, 2017 https://doi.org/10.1002/cncr.31039
  27. Munakata K, Uemura M, Tanaka S, Kawai K, Kitahara T, Miyo M, et al. : Cancer stem-like properties in colorectal cancer cells with low proteasome activity. Clin Cancer Res 22 : 5277-5286, 2016 https://doi.org/10.1158/1078-0432.CCR-15-1945
  28. Neguembor MV, Xynos A, Onorati MC, Caccia R, Bortolanza S, Godio C, et al. : FSHD muscular dystrophy region gene 1 binds suv4-20h1 histone methyltransferase and impairs myogenesis. J Mol Cell Biol 5 : 294-307, 2013 https://doi.org/10.1093/jmcb/mjt018
  29. O'Brien AJ, Villani LA, Broadfield LA, Houde VP, Galic S, Blandino G, et al. : Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis. Biochem J 469 : 177-187, 2015 https://doi.org/10.1042/BJ20150122
  30. Pan SJ, Ren J, Jiang H, Liu W, Hu LY, Pan YX, et al. : MAGEA6 promotes human glioma cell survival via targeting AMPKα1. Cancer Lett 412 : 21-29, 2018 https://doi.org/10.1016/j.canlet.2017.09.051
  31. Pei S, Minhajuddin M, Adane B, Khan N, Stevens BM, Mack SC, et al. : AMPK/FIS1-mediated mitophagy is required for self-renewal of human AML stem cells. Cell Stem Cell 23 : 86-100, 2018 https://doi.org/10.1016/j.stem.2018.05.021
  32. Peng Z, Liu C, Wu M : New insights into long noncoding RNAs and their roles in glioma. Mol Cancer 17 : 61, 2018 https://doi.org/10.1186/s12943-018-0812-2
  33. Quinones A, Le A : The multifaceted metabolism of glioblastoma. Adv Exp Med Biol 1063 : 59-72, 2018 https://doi.org/10.1007/978-3-319-77736-8_4
  34. Sharples AP, Hughes DC, Deane CS, Saini A, Selman C, Stewart CE : Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake. Aging Cell 14 : 511-523, 2015 https://doi.org/10.1111/acel.12342
  35. Smith BK, Marcinko K, Desjardins EM, Lally JS, Ford RJ, Steinberg GR : Treatment of nonalcoholic fatty liver disease: role of AMPK. Am J Physiol Endocrinol Metab 311 : E730-E740, 2016 https://doi.org/10.1152/ajpendo.00225.2016
  36. Umezawa S, Higurashi T, Nakajima A : AMPK: therapeutic target for diabetes and cancer prevention. Curr Pharm Des 23 : 3629-3644, 2017
  37. Wang C, Tong Y, Wen Y, Cai J, Guo H, Huang L, et al. : Hepatocellular carcinoma-associated protein TD26 interacts and enhances sterol regulatory element-binding protein 1 activity to promote tumor cell proliferation and growth. Hepatology 68 : 1833-1850, 2018 https://doi.org/10.1002/hep.30030
  38. Weller M, Van den Bent M, Tonn JC, Stupp R, Preusser M, CohenJonathan-Moyal E, et al. : European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 18 : e315-e329, 2017 https://doi.org/10.1016/S1470-2045(17)30194-8
  39. Xu L, Kong L, Wang J, Ash JD : Stimulation of AMPK prevents degeneration of photoreceptors and the retinal pigment epithelium. Proc Natl Acad Sci U S A 115 : 10475-10480, 2018 https://doi.org/10.1073/pnas.1802724115
  40. Zhao W, Peng F, Shu M, Liu H, Hou X, Wang X, et al. : Isogambogenic acid inhibits the growth of glioma through activation of the AMPKmTOR pathway. Cell Physiol Biochem 44 : 1381-1395, 2017 https://doi.org/10.1159/000485535
  41. Zhao Y, Hu X, Liu Y, Dong S, Wen Z, He W, et al. : ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway. Mol Cancer 16 : 79, 2017 https://doi.org/10.1186/s12943-017-0648-1