Ukr.Biochem.J. 2018; Том 90, № 3, травень-червень, c. 49-61
doi: https://doi.org/10.15407/ubj90.03.049
IRE1 змінює ефект дефіциту глутаміну на експресію факторів росту пухлин у клітинах гліоми лінії U87
О. Г. Мінченко, А. П. Харькова, О. С. Гнатюк,
О. Я. Лузіна, І. В. Кривдюк, А. Ю. Кузнєцова
Інститут біохімії ім. О. В. Палладіна НАН України, Київ;
e-mail: ominchenko@yahoo.com
У роботі досліджували експресію групи генів, що кодують важливі протеїни в клітинах гліоми лінії U87 в умовах пригнічення функції ERN1 (endoplasmic reticulum to nucleus signaling 1) та дефіциту глутаміну. Показано, що за умов дефіциту глутаміну знижувався рівень експресії мРНК ATF6 (activating transcription factor 6), EIF2AK3/PERK (eukaryotic translation initiation factor 2 alpha kinase 3), GLO1 (glyoxalase I), BIRC5 (baculoviral IAP repeat-containing 5) та RAB5C (RAB5C, a member of RAS oncogene family) в контрольних клітинах гліоми. В той самий час, рівень експресії мРНК HSPB8 (heat shock 22 kDa protein 8) та HSPA5/GRP78 (heat shock protein family A (Hsp70) member 5) був резистентним до дефіциту глутаміну в цих клітинах гліоми. Пригнічення ERN1 модифікувало ефект дефіциту глутаміну на рівень експресії більшості досліджених генів у клітинах гліоми лінії U87: збільшувало експресію генів ATF6 і HSPA5 та посилювало чутливість генів EIF2AK3 і BIRC5 до дефіциту глутаміну. Більше того, експресія досліджених генів (за винятком EIF2AK3) знижувалася в клітинах гліоми з пригніченим ERN1 у присутності глутаміну. Показано, що дефіцит глутаміну змінює експресію більшості досліджених генів залежно від ERN1 і ці зміни, можливо, причетні до пригнічення росту гліом із клітин без функціональної активності сигнального ензиму ERN1.
Ключові слова: ATF6, BIRC5, EIF2AK3, HSPA5, RAB5C, дефіцит глутаміну, експресія мРНК, клітини гліоми лінії U87, пригнічення ERN1
Посилання:
- Lieberman F. Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials. F1000Res. 2017 Oct 26;6:1892. PubMed, PubMedCentral, CrossRef
- Pearson JRD, Regad T. Targeting cellular pathways in glioblastoma multiforme. Signal Transduct Target Ther. 2017 Sep 29;2:17040. PubMed, PubMedCentral, CrossRef
- Lara-Velazquez M, Al-Kharboosh R, Jeanneret S, Vazquez-Ramos C, Mahato D, Tavanaiepour D, Rahmathulla G, Quinones-Hinojosa A. Advances in Brain Tumor Surgery for Glioblastoma in Adults. Brain Sci. 2017 Dec 20;7(12). pii: E166. PubMed, PubMedCentral, CrossRef
- Galmiche A, Sauzay C, Chevet E, Pluquet O. Role of the unfolded protein response in tumor cell characteristics and cancer outcome. Curr Opin Oncol. 2017 Jan;29(1):41-47. PubMed, CrossRef
- Obacz J, Avril T, Le Reste PJ, Urra H, Quillien V, Hetz C, Chevet E. Endoplasmic reticulum proteostasis in glioblastoma-From molecular mechanisms to therapeutic perspectives. Sci Signal. 2017 Mar 14;10(470). pii: eaal2323. PubMed, CrossRef
- Valdés-Rives SA, Casique-Aguirre D, Germán-Castelán L, Velasco-Velázquez MA, González-Arenas A. Apoptotic Signaling Pathways in Glioblastoma and Therapeutic Implications. Biomed Res Int. 2017;2017:7403747. PubMed, PubMedCentral, CrossRef
- Auf G, Jabouille A, Delugin M, Guérit S, Pineau R, North S, Platonova N, Maitre M, Favereaux A, Vajkoczy P, Seno M, Bikfalvi A, Minchenko D, Minchenko O, Moenner M. High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor. BMC Cancer. 2013 Dec 13;13:597. PubMed, PubMedCentral, CrossRef
- Minchenko OH, Tsymbal DO, Minchenko DO. IRE-1alpha signaling as a key target for suppression of tumor growth. Single Cell Biol. 2015; 4(3): 118. CrossRef
- Lhomond S, Avril T, Dejeans N, Voutetakis K, Doultsinos D, McMahon M, Pineau R, Obacz J, Papadodima O, Jouan F, Bourien H, Logotheti M, Jégou G, Pallares-Lupon N, Schmit K, Le Reste PJ, Etcheverry A, Mosser J, Barroso K, Vauléon E, Maurel M, Samali A, Patterson JB, Pluquet O, Hetz C, Quillien V, Chatziioannou A, Chevet E. Dual IRE1 RNase functions dictate glioblastoma development. EMBO Mol Med. 2018 Jan 8. pii: e7929. PubMed, PubMedCentral, CrossRef
- Chevet E, Hetz C, Samali A. Endoplasmic reticulum stress-activated cell reprogramming in oncogenesis. Cancer Discov. 2015 Jun;5(6):586-97. PubMed, CrossRef
- Minchenko DО, Kubaichuk КІ, Ratushna OO, Komisarenko SV, Minchenko OH. The vascular endothelial growth factor genes expression in glioma U87 cells is dependent from ERN1 signaling enzyme function. Adv Biol Chem. 2012; 2(2): 198-206. CrossRef
- Auf G, Jabouille A, Guérit S, Pineau R, Delugin M, Bouchecareilh M, Magnin N, Favereaux A, Maitre M, Gaiser T, von Deimling A, Czabanka M, Vajkoczy P, Chevet E, Bikfalvi A, Moenner M. Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci USA. 2010 Aug 31;107(35):15553-8. PubMed, PubMedCentral, CrossRef
- Minchenko OH, Tsymbal DO, Minchenko DO, Moenner M, Kovalevska OV, Lypova NM. Inhibition of kinase and endoribonuclease activity of ERN1/IRE1α affects expression of proliferationrelated genes in U87 glioma cells. Endoplasm Reticul Stress Dis. 2015; 2(1): 18-29. CrossRef
- Minchenko DO, Riabovol OO, Ratushna OO, Minchenko OH. Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition. Endocr Regul. 2017 Jan 1;51(1):8-19. PubMed, CrossRef
- Alberghina L, Gaglio D. Redox control of glutamine utilization in cancer. Cell Death Dis. 2014 Dec 4;5:e1561. PubMed, PubMedCentral, CrossRef
- Yang S, Hwang S, Kim M, Seo SB, Lee JH, Jeong SM. Mitochondrial glutamine metabolism via GOT2 supports pancreatic cancer growth through senescence inhibition. Cell Death Dis. 2018 Jan 19;9(2):55. PubMed, PubMedCentral, CrossRef
- Polet F, Corbet C, Pinto A, Rubio LI, Martherus R, Bol V, Drozak X, Grégoire V, Riant O, Feron O. Reducing the serine availability complements the inhibition of the glutamine metabolism to block leukemia cell growth. Oncotarget. 2016 Jan 12;7(2):1765-76. PubMed, PubMedCentral, CrossRef
- Ma L, Tao Y, Duran A, Llado V, Galvez A, Barger JF, Castilla EA, Chen J, Yajima T, Porollo A, Medvedovic M, Brill LM, Plas DR, Riedl SJ, Leitges M, Diaz-Meco MT, Richardson AD, Moscat J. Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis. Cell. 2013 Jan 31;152(3):599-611. PubMed, PubMedCentral, CrossRef
- Tsymbal DO, Minchenko DO, Kryvdiuk IV, Riabovo OO, Halkin OO, Ratushna OO, Minchenko OH. Expression of proliferation related transcription factor genes in U87 glioma cells with IRE1 knockdown: upon glucose and glutamine deprivation. Fiziol Zh. 2016;62(1):3-15. PubMed, CrossRef
- Tsymbal DO, Minchenko DO, Riabovol OO, Ratushna OO, Minchenko OH. IRE1 knockdown modifies glucose and glutamine deprivation effects on the expression of proliferation related genes in U87 glioma cells. Biotechnol Acta. 2016; 9(1): 26-37. CrossRef
- Riabovol OO, Tsymbal DO, Minchenko DO, Ratushna OO, Minchenko OH. IRE1 knockdown modifies the glutamine and glucose deprivation effect on the expression of nuclear genes encoding mitochondrial proteins in U87 glioma cells. Biotechnol Acta. 2016; 9(2): 37-47. CrossRef
- Minchenko OH, Kharkova AP, Minchenko DO, Karbovskyi LL. Expression of IGFBP6, IGFBP7, NOV, CYR61, WISP1 and WISP2 genes in U87 glioma cells in glutamine deprivation condition. Ukr Biochem J. 2016 May-Jun;88(3):66-77. PubMed, CrossRef
- Halkin OV, Minchenko DO, Riabovol OO, Telychko VV, Ratushna OO, Minchenko OH. Expression of ubiquitin specific peptidase and ATG7 genes in U87 glioma cells upon glutamine deprivation. Ukr Biochem J. 2017; 89(5): 52-61. CrossRef
- Bu LJ, Yu HQ, Fan LL, Li XQ, Wang F, Liu JT, Zhong F, Zhang CJ, Wei W, Wang H, Sun GP. Melatonin, a novel selective ATF-6 inhibitor, induces human hepatoma cell apoptosis through COX-2 downregulation. World J Gastroenterol. 2017 Feb 14;23(6):986-998. PubMed, PubMedCentral, CrossRef
- Tungkum W, Jumnongprakhon P, Tocharus C, Govitrapong P, Tocharus J. Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines. J Toxicol Sci. 2017;42(1):63-71. PubMed, CrossRef
- Druelle C, Drullion C, Deslé J, Martin N, Saas L, Cormenier J, Malaquin N, Huot L, Slomianny C, Bouali F, Vercamer C, Hot D, Pourtier A, Chevet E, Abbadie C, Pluquet O. ATF6α regulates morphological changes associated with senescence in human fibroblasts. Oncotarget. 2016 Oct 18;7(42):67699-67715. PubMed, PubMedCentral, CrossRef
- Zhang M, Liu X, Wang Q, Ru Y, Xiong X, Wu K, Yao L, Li X. NDRG2 acts as a PERK co-factor to facilitate PERK branch and ERS-induced cell death. FEBS Lett. 2017 Nov;591(21):3670-3681. PubMed, CrossRef
- Wang SQ, Wang X, Zheng K, Liu KS, Wang SX, Xie CH. Simultaneous targeting PI3K and PERK pathways promotes cell death and improves the clinical prognosis in esophageal squamous carcinoma. Biochem Biophys Res Commun. 2017 Nov 4;493(1):534-541. PubMed, CrossRef
- Márton M, Kurucz A, Lizák B, Margittai É, Bánhegyi G, Kapuy O. A Systems Biological View of Life-and-Death Decision with Respect to Endoplasmic Reticulum Stress-The Role of PERK Pathway. Int J Mol Sci. 2017 Jan 5;18(1). pii: E58. PubMed, PubMedCentral, CrossRef
- Guo Y, Zhang Y, Yang X, Lu P, Yan X, Xiao F, Zhou H, Wen C, Shi M, Lu J, Meng QH. Effects of methylglyoxal and glyoxalase I inhibition on breast cancer cells proliferation, invasion, and apoptosis through modulation of MAPKs, MMP9, and Bcl-2. Cancer Biol Ther. 2016;17(2):169-80. PubMed, PubMedCentral, CrossRef
- Geng X, Ma J, Zhang F, Xu C. Glyoxalase I in tumor cell proliferation and survival and as a potential target for anticancer therapy. Oncol Res Treat. 2014;37(10):570-4. PubMed, CrossRef
- Chiavarina B, Nokin MJ, Bellier J, Durieux F, Bletard N, Sherer F, Lovinfosse P, Peulen O, Verset L, Dehon R, Demetter P, Turtoi A, Uchida K, Goldman S, Hustinx R, Delvenne P, Castronovo V, Bellahcène A. Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer. Int J Mol Sci. 2017 Jan 21;18(1). pii: E213. PubMed, PubMedCentral, CrossRef
- Hutschenreuther A, Bigl M, Hemdan NY, Debebe T, Gaunitz F, Birkenmeier G. Modulation of GLO1 Expression Affects Malignant Properties of Cells. Int J Mol Sci. 2016 Dec 18;17(12). pii: E2133. PubMed, PubMedCentral, CrossRef
- Antognelli C, Gambelunghe A, Muzi G, Talesa VN. Glyoxalase I drives epithelial-to-mesenchymal transition via argpyrimidine-modified Hsp70, miR-21 and SMAD signalling in human bronchial cells BEAS-2B chronically exposed to crystalline silica Min-U-Sil 5: Transformation into a neoplastic-like phenotype. Free Radic Biol Med. 2016 Mar;92:110-125. PubMed, CrossRef
- Wang C, Cai L, Liu J, Wang G, Li H, Wang X, Xu W, Ren M, Feng L, Liu P, Zhang C. MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression. Cell Physiol Biochem. 2017;43(6):2405-2419. PubMed, CrossRef
- Kang JM, Park S, Kim SJ, Kim H, Lee B, Kim J, Park J, Kim ST, Yang HK, Kim WH, Kim SJ. KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78. Cancer Res. 2015 Aug 1;75(15):3087-97. PubMed, CrossRef
- Piccolella M, Crippa V, Cristofani R, Rusmini P, Galbiati M, Cicardi ME, Meroni M, Ferri N, Morelli FF, Carra S, Messi E, Poletti A. The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells. Oncotarget. 2017 Feb 7;8(6):10400-10415. PubMed, PubMedCentral, CrossRef
- Li XS, Xu Q, Fu XY, Luo WS. Heat shock protein 22 overexpression is associated with the progression and prognosis in gastric cancer. J Cancer Res Clin Oncol. 2014 Aug;140(8):1305-13. PubMed, CrossRef
- Acunzo J, Katsogiannou M, Rocchi P. Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. Int J Biochem Cell Biol. 2012 Oct;44(10):1622-31. PubMed, CrossRef
- de Graaff MA, Malu S, Guardiola I, Kruisselbrink AB, de Jong Y, Corver WE, Gelderblom H, Hwu P, Nielsen TO, Lazar AJ, Somaiah N, Bovée JVMG. High-Throughput Screening of Myxoid Liposarcoma Cell Lines: Survivin Is Essential for Tumor Growth. Transl Oncol. 2017 Aug;10(4):546-554. PubMed, PubMedCentral, CrossRef
- Igarashi T, Araki K, Yokobori T, Altan B, Yamanaka T, Ishii N, Tsukagoshi M, Watanabe A, Kubo N, Handa T, Hosouchi Y, Nishiyama M, Oyama T, Shirabe K, Kuwano H. Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression. Oncotarget. 2017 Feb 14;8(7):12290-12300. PubMed, PubMedCentral, CrossRef
- Tan YS, Kim M, Kingsbury TJ, Civin CI, Cheng WC. Regulation of RAB5C is important for the growth inhibitory effects of MiR-509 in human precursor-B acute lymphoblastic leukemia. PLoS One. 2014 Nov 4;9(11):e111777. PubMed, PubMedCentral, CrossRef
- Bochkov VN, Philippova M, Oskolkova O, Kadl A, Furnkranz A, Karabeg E, Afonyushkin T, Gruber F, Breuss J, Minchenko A, Mechtcheriakova D, Hohensinner P, Rychli K, Wojta J, Resink T, Erne P, Binder BR, Leitinger N. Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a novel role for lipid oxidation in the evolution of atherosclerotic lesions. Circ Res. 2006 Oct 13;99(8):900-8. PubMed, CrossRef
- Manié SN, Lebeau J, Chevet E. Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update. Am J Physiol Cell Physiol. 2014 Nov 15;307(10):C901-7. PubMed, CrossRef
- Lukey MJ, Greene KS, Erickson JW, Wilson KF, Cerione RA. The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy. Nat Commun. 2016 Apr 18;7:11321. PubMed, PubMedCentral, CrossRef
- Chen L, Cui H. Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach. Int J Mol Sci. 2015 Sep 22;16(9):22830-55. PubMed, PubMedCentral, CrossRef
This work is licensed under a Creative Commons Attribution 4.0 International License.