Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Endoplasmic Reticulum Stress in Diseases

Ed. by Blumental-Perry, Anna / Wang, X. Robert

1 Issue per year


Emerging Science

Open Access
Online
ISSN
2300-4266
See all formats and pricing
Online
Open Access
*Prices in US$ apply to orders placed in the Americas only. Prices in GBP apply to orders placed in Great Britain only. Prices in € represent the retail prices valid in Germany (unless otherwise indicated). Prices are subject to change without notice. Prices do not include postage and handling if applicable. RRP: Recommended Retail Price.
More options …

Inhibition of kinase and endoribonuclease activity of ERN1/IRE1α affects expression of proliferation related genes in U87 glioma cells

Oleksandr H. Minchenko
  • Corresponding author
  • Department of Molecular Biology, Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, 9 Leontovycha St., 01601, Kyiv, Ukraine
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
 / Dariia O. Tsymbal
  • Corresponding author
  • Department of Molecular Biology, Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, 9 Leontovycha St., 01601, Kyiv, Ukraine
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
 / Dmytro O. Minchenko
  • Corresponding author
  • Department of Molecular Biology, Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, 9 Leontovycha St., 01601, Kyiv, Ukraine
  • Departments of Pediatrics, Bogomolets National Medical University, 13 Shevchenka Bvld., 01601, Kyiv, Ukraine
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
 / Michel Moenner
  • Corresponding author
  • INSERM U1029 Angiogenesis and Cancer Microenvironment Laboratory, University Bordeaux 1, Talence 33405, France
  • Université de Bordeaux, IBGC UMR 5095 1, F-33077 Bordeaux, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
 / Olena V. Kovalevska
  • Corresponding author
  • Department of Molecular Biology, Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, 9 Leontovycha St., 01601, Kyiv, Ukraine
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
 / Nadia M. Lypova
  • Corresponding author
  • Department of Molecular Biology, Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, 9 Leontovycha St., 01601, Kyiv, Ukraine
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-02-25 | DOI: https://doi.org/10.1515/ersc-2015-0002

Open Access

Download PDF

Abstract

Inhibition of ERN1/IRE1α (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme-1α), the major signaling pathway of endoplasmic reticulum stress, significantly decreases tumor growth. We have studied the expression of transcription factors such as E2F8 (E2F transcription factor 8), EPAS1 (endothelial PAS domain protein 1), TBX3 (T-box 3), ATF3 (activating transcription factor 3), FOXF1 (forkhead box F1), and HOXC6 (homeobox C6) in U87 glioma cells overexpressing dominant-negative ERN1/IRE1α defective in endoribonuclease (dnr-ERN1) as well as defective in both kinase and endonuclease (dn-ERN1) activity of ERN1/IRE1α. We have demonstrated that the expression of all studied genes is decreased at the mRNA level in cells with modified ERN1/IRE1α; TBX3, however, is increased in these cells as compared to control glioma cells. Changes in protein levels of E2F8, HOXC6, ATF3, and TBX3 corresponded to changes in mRNAs levels. We also found that two mutated ERN1/IRE1α have differential effects on the expression of studied transcripts. The presence of kinase and endonuclease deficient ERN1/IRE1α in glioma cells had a less profound effect on the expression of E2F8, HOXC6, and TBX3 genes than the blockade of the endoribonuclease activity of ERN1/IRE1α alone. Kinase and endonuclease deficient ERN1/IRE1α suppresses ATF3 and FOXF1 gene expressions, while inhibition of only endoribonuclease of ERN1/IRE1α leads to the up-regulation of these gene transcripts. The present study demonstrates that fine-tuning of the expression of proliferation related genes is regulated by ERN1/IRE1α an effector of endoplasmic reticulum stress. Inhibition of ERN1/IRE1α, especially its endoribonuclease activity, correlates with deregulation of proliferation related genes and thus slower tumor growth.

Keywords : endoplasmic reticulum stress; ERN1/IRE1α; E2F8; EPAS1; HOXC6; ATF3; TBX3; FOXF1; U87 glioma cells; NHA/TS astrocyte cells

References

  • [1] Zhang K, Kaufman RJ. The unfolded protein response: a stress signaling pathway critical for health and disease. Neurology 2006; 66 (Suppl 1): S102–9. CrossrefGoogle Scholar

  • [2] Moenner M, Pluquet O, Bouchecareilh M, Chevet E. Integrated endoplasmic reticulum stress responses in cancer. Cancer Res 2007; 67: 10631–4. Web of ScienceCrossrefGoogle Scholar

  • [3] Wang S, Kaufman RJ. The impact of the unfolded protein response on human disease. J Cell Biol 2012; 197: 857-67. Web of ScienceGoogle Scholar

  • [4] Schröder M. Endoplasmic reticulum stress responses. Cell Mol Life Sci 2008 65: 862–94. Web of ScienceCrossrefGoogle Scholar

  • [5] Malhotra JD, Kaufman RJ. ER stress and its functional link to mitochondria: role in cell survival and death. Cold Spring Harb Perspect Biol 2011; 3: a004424. Google Scholar

  • [6] Lenihan CR, Taylor CT. The impact of hypoxia on cell death pathways. Biochem Soc Trans 2013; 41: 657–63. CrossrefWeb of ScienceGoogle Scholar

  • [7] Minchenko OH, Kharkova AP, Bakalets TV, Kryvdiuk IV. Endoplasmic reticulum stress, its sensor and signaling systems and the role in the regulation of gene expressions in malignant tumor growth and hypoxia. Ukr Biochem J 2013; 85(5): 5–16. CrossrefGoogle Scholar

  • [8] Hollien J, Lin JH, Li H, Stevens N, Walter P, Weissman JS. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol 2009; 186: 323–31. Google Scholar

  • [9] Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, Arias C, Lennon CJ, Kluger Y, Dynlacht DD. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Molecular Cell 2007; 27: 53–66. CrossrefGoogle Scholar

  • [10] Aragón T, van Anken E, Pincus D., Serafimova IM, Korennykh AV, Rubio CA, Walter P. Messenger RNA targeting to endoplasmic reticulum stress signalling sites. Nature. 2009; 457: 736–40. Web of ScienceGoogle Scholar

  • [11] Pluquet O, Dejeans N, Bouchecareilh M, Lhomond S, Pineau R, Higa A, Delugin M, Combe C, Loriot S, Cubel G, Dugot-Senant N, Vital A, Loiseau H, Gosline SJ, Taouji S, Hallett M, Sarkaria JN, Anderson K, Wu W, Rodriguez FJ, Rosenbaum J, Saltel F, Fernandez-Zapico ME, Chevet E. Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα. Cancer Res. 2013; 73: 4732–43. Google Scholar

  • [12] Minchenko OH, Kubaichuk KI, Minchenko DO, Kovalevska OV, Kulinich AO, Lypova NM. Molecular mechanisms of ERN1-mediated angiogenesis. Int J Physiol Pathophysiol 2014; 5: 1-22. CrossrefGoogle Scholar

  • [13] Drogat B, Auguste P, Nguyen DT, Bouchecareilh M, Pineau R, Nalbantoglu J, Kaufman RJ, Chevet E, Bikfalvi A, Moenner M. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer Res 2007; 67: 6700–7. CrossrefGoogle Scholar

  • [14] Auf G, Jabouille A, Guerit 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. Inositolrequiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci USA 2010; 107: 15553–8. Google Scholar

  • [15] 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 IRE1alpha and promotes autocrine growth through EGF receptor. BMC Cancer 2013; 13: 597. CrossrefGoogle Scholar

  • [16] Washkowitz AJ, Gavrilov S, Begum S, Papaioannou VE. Diverse functional networks of Tbx3 in development and disease. Wiley Interdiscip Rev Syst Biol Med 2012; 4: 273-83. CrossrefGoogle Scholar

  • [17] Deng Q, Wang Q, Zong WY, Zheng DL, Wen YX, Wang KS, Teng XM, Zhang X, Huang J, Han ZG. E2F8 contributes to human hepatocellular carcinoma via regulating cell proliferation. Cancer Res 2010; 70: 782-91. Web of ScienceGoogle Scholar

  • [18] Liu J, Edagawa M, Goshima H, Inoue M, Yagita H, Liu Z, Kitajima S Role of ATF3 in synergistic cancer cell killing by a combination of HDAC inhibitors and agonistic anti-DR5 antibody through ER stress in human colon cancer cells. Biochem Biophys Res Commun 2014; 445: 320-6. Google Scholar

  • [19] Raspaglio G, Petrillo M, Martinelli E, Li Puma DD, Mariani M, De Donato M, Filippetti F, Mozzetti S, Prislei S, Zannoni GF, Scambia G, Ferlini C. Sox9 and Hif-2α regulate TUBB3 gene expression and affect ovarian cancer aggressiveness. Gene 2014; 542: 173-81. Google Scholar

  • [20] Rizzardi AE, Rosener NK, Koopmeiners JS, Isaksson Vogel R, Metzger GJ, Forster CL, Marston LO, Tiffany JR, McCarthy JB, Turley EA, Warlick CA, Henriksen JC, Schmechel SC. Evaluation of protein biomarkers of prostate cancer aggressiveness. BMC Cancer 2014; 14: 244. CrossrefWeb of ScienceGoogle Scholar

  • [21] Katoh M, Igarashi M, Fukuda H, Nakagama H, Katoh M. Cancer genetics and genomics of human FOX family genes. Cancer Lett 2013; 328: 198-206. Web of ScienceGoogle Scholar

  • [22] Weijts BG, Bakker WJ, Cornelissen PW, Liang KH, Schaftenaar FH, Westendorp B, de Wolf CA, Paciejewska M, Scheele CL, Kent L, Leone G, Schulte-Merker S, de Bruin A. E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1. EMBO J 2012; 31: 3871-84. CrossrefGoogle Scholar

  • [23] Christensen J, Cloos P, Toftegaard U, Klinkenberg D, Bracken AP, Trinh E, Heeran M, Di Stefano L, Helin K. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription. Nucl Acids Res 2005; 33: 5458-70. CrossrefGoogle Scholar

  • [24] Li J, Weinberg MS, Zerbini L, Prince S. The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway. Mol Biol Cell 2013; 24: 3569-76. CrossrefGoogle Scholar

  • [25] Du YB, Dong B, Shen LY, Yan WP, Dai L, Xiong HC, Liang Z, Kang XZ, Qin B, Chen KN. The survival predictive significance of HOXC6 and HOXC8 in esophageal squamous cell carcinoma. J Surg Res 2014; 188: 442-50. Google Scholar

  • [26] Zhang Q, Jin XS, Yang ZY, Wei M, Liu BY, Gu QL. Upregulated Hoxc6 expression is associated with poor survival in gastric cancer patients. Neoplasma 2013; 60: 439-45. Google Scholar

  • [27] Tamura M, Sasaki Y, Koyama R, Takeda K, Idogawa M, Tokino T. Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness. Oncogene. 2014; 33: 4837-46. Google Scholar

  • [28] Wei S, Wang H, Lu C, Malmut S, Zhang J, Ren S, Yu G, Wang W, Tang DD and Yan C. The activating transcription factor 3 protein suppresses the oncogenic function of mutant p53 proteins. J Biol Chem 2014; 289: 8947-59. Web of ScienceGoogle Scholar

  • [29] Wu ZY, Wei ZM, Sun SJ, Yuan J, Jiao SC. Activating transcription factor 3 promotes colon cancer metastasis. Tumour Biol 2014; 35(8):8329-34. CrossrefGoogle Scholar

  • [30] Feng J, Sun Q, Wu T, Lu J, Qu L, Sun Y, Tian L, Zhang B, Li D, Liu M. Upregulation of ATF-3 is correlated with prognosis and proliferation of laryngeal cancer by regulating Cyclin D1 expression. Int J Clin Exp Pathol 2013; 6: 2064-70. Google Scholar

  • [31] Sato A, Nakama K, Watanabe H, Satake A, Yamamoto A, Omi T, Hiramoto A, Masutani M, Wataya Y, Kim HS. Role of activating transcription factor 3 protein ATF3 in necrosis and apoptosis induced by 5-fluoro-2’-deoxyuridine. FEBS J 2014; 281: 1892-900. Google Scholar

  • [32] Ahmad A, Ahmad S, Malcolm KC, Miller SM, Hendry-Hofer T, Schaack JB, White CW. Differential regulation of pulmonary vascular cell growth by hypoxia-inducible transcription factor-1alpha and hypoxia-inducible transcription factor-2alpha. Am J Respir Cell Mol Biol 2013; 49: 78-85. Web of ScienceGoogle Scholar

  • [33] Bangoura G, Yang LY, Huang GW, Wang W. Expression of HIF-2alpha/ EPAS1 in hepatocellular carcinoma. World J Gastroenterol 2004; 10: 525-30. CrossrefGoogle Scholar

  • [34] Sasai K, Akagi T, Aoyanagi E, Tabu K, Kaneko S, Tanaka S. O6-methylguanine-DNA methyltransferase is downregulated in transformed astrocyte cells: implications for anti-glioma therapies. Mol Cancer 2007, 6: 36. Web of ScienceGoogle Scholar

  • [35] Minchenko DO, Danilovskyi SV, Kryvdiuk IV, Bakalets TV, Lypova NM, Karbovskyi LL, Minchenko OH. Inhibition of ERN1 modifies the hypoxic regulation of the expression of TP53-related genes in U87 glioma cells. Endoplasmic Reticulum Stress in Diseases 2014; 1: 18-26. Google Scholar

  • [36] Minchenko DО, Kubajchuk КІ, Ratushna OO, Komisarenko SV, Minchenko OH. The effect of hypoxia and ischemic condition on the expression of VEGF genes in glioma U87 cells is dependent from ERN1 knockdown. Adv Biol Chem 2012; 2: 198-206. CrossrefGoogle Scholar

  • [37] Minchenko OH, Opentanova IL, Minchenko DO, Ogura T, Esumi H. Hypoxia induces transcription of 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase 4 gene via hypoxia-inducible factor- 1alpha activation. FEBS Lett 2004; 576: 14-20. Google Scholar

  • [38] Bochkov VN, Philippova M, Oskolkova O, Kadl A, Furnkranz A, Karabeg E, Breuss J, Minchenko OH, Mechtcheriakova D, Hohensinner P, Rychli K, Wojta J, Resink T, Binder BR, Leitinger N. Oxidized phospholipids stimulate angiogenesis via induction of VEGF, IL-8, COX-2 and ADAMTS-1 metalloprotease, implicating a novel role for lipid oxidation in progression and destabilization of atherosclerotic lesions. Circ Res 2006; 99: 900-8. Google Scholar

  • [39] Melboucy-Belkhir S, Pradère P, Tadbiri S, Habib S, Bacrot A, Brayer S, Mari B, Besnard V, Mailleux AA, Guenther A, Castier Y, Mal H, Crestani B, Plantier L. Forkhead Box F1 (FOXF1) represses cell growth, COL1 and ARPC2 expression in lung fibroblasts in vitro. Am J Physiol Lung Cell Mol Physiol. 2014; 307: L838-47. Google Scholar

  • [40] Backer MV, Backer JM, Chinnaiyan P. Targeting the unfolded protein response in cancer therapy. Methods Enzymol. 2011; 491: 37–56. Web of ScienceGoogle Scholar

  • [41] Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res. 2007; 67: 3496–9. CrossrefGoogle Scholar

  • [42] Johnson GG, White MC, Grimaldi M. Stressed to death: targeting endoplasmic reticulum stress response induced apoptosis in gliomas. Curr Pharm Des. 2011; 17: 284-92. CrossrefGoogle Scholar

  • [43] Endo Y, Uzawa K, Mochida Y, Shiiba M, Bukawa H, Yokoe H, Tanzawa H. Sarcoendoplasmic reticulum Ca(2+) ATPase type 2 downregulated in human oral squamous cell carcinoma. Int J Cancer. 2004; 110: 225-31. Google Scholar

  • [44] White MC, Johnson GG, Zhang W, Hobrath JV, Piazza GA, Grimaldi M. Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca(2+) ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: Relevant similarities to and important differences from celecoxib. J Neurosci Res. 2013; 91: 393-406. Int J Cancer. 2004; 110: 225-31. Google Scholar

  • [45] Ciechomska IA, Gabrusiewicz K, Szczepankiewicz AA, Kaminska B. Endoplasmic reticulum stress triggers autophagy in malignant glioma cells undergoing cyclosporine a-induced cell death. Oncogene. 2013; 32: 1518-29. Web of ScienceCrossrefGoogle Scholar

About the article

Received: 2014-08-20

Accepted: 2014-12-22

Published Online: 2015-02-25

Citation Information: Endoplasmic Reticulum Stress in Diseases, Volume 2, Issue 1, ISSN (Online) 2300-4266, DOI: https://doi.org/10.1515/ersc-2015-0002.

Export Citation

© 2015 Oleksandr H. Minchenko et al.. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
M.S. Kharchuk
Biotechnologia Acta, 2017, Volume 10, Number 6, Page 28
[2]
O. H. Minchenko
Biotechnologia Acta, 2016, Volume 9, Number 6, Page 16
[3]
O. H. Minchenko
Biotechnologia Acta, 2016, Volume 9, Number 5, Page 7
[4]
O. H. Minchenko, D. O. Tsymbal, D. O. Minchenko, and O. O. Kubaychuk
The Ukrainian Biochemical Journal, 2016, Volume 88, Number 6, Page 52
[5]
O. H. Minchenko, A. P. Kharkova, D. O. Minchenko, and L. L. Karbovskyi
The Ukrainian Biochemical Journal, 2016, Volume 88, Number 3, Page 66
[6]
O. H. Minchenko, D. O. Tsymbal, and D. O. Minchenko
The Ukrainian Biochemical Journal, 2016, Volume 88, Number 1, Page 11
[7]
I. V. Kryvdiuk, D. O. Minchenko, and N. A. Hlushchak
The Ukrainian Biochemical Journal, 2015, Volume 87, Number 6, Page 36
[8]
O. H. Minchenko, A. P. Kharkova, D. O. Minchenko, and L. L. Karbovskyi
The Ukrainian Biochemical Journal, 2015, Volume 87, Number 6, Page 52

Comments (0)

Please log in or register to comment.
Log in