ВПЛИВ ДЕФІЦИТУ ПОЖИВНИХ РЕЧОВИН НА ЕКСПРЕСІЮ ГЕНІВ PDGFC, PDGFRA ТА PDGFRB У КЛІТИНАХ ГЛІОМИ ЛІНІЇ U87 ЗАЛЕЖИТЬ ВІД ФУНКЦІЇ СИГНАЛЬНОГО ЕНЗИМУ ERN1
Анотація
Фактори росту, що контролюють ангіогенез, відіграють важливу роль у рості злоякісних пухлин. Ми вивчали вплив дефіциту глюкози і глутаміну на рівень експресії мРНК PDGFC (platelet derived growth factor C) та його рецепторів PDGFRA (platelet derived growth factor receptor A) and PDGFRB у клітинах гліоми лінії U87. Встановлено, що пригнічення обох ензиматичних активностей сенсорно-сигнального ензиму ERN1 (endoplasmic reticulum to nucleus signaling 1), основного сигнального компоненту стресу ендоплазматичного ретикулуму, підвищує рівень експресії генів, що кодують PDGFC, PDGFRA та PDGFRB у клітинах гліоми лінії U87. За умов дефіциту глутаміну спостерігається збільшення рівня експресії гена PDGFC та зменшення – генів PDGFRA і PDGFRB у контрольних клітинах гліоми, але виключення ERN1 модифікує ефект дефіциту глутаміну на експресію цих генів. Було також показано, що за умов дефіциту глюкози рівень експресії гена PDGFC істотно не змінюється у контрольних клітинах гліоми, але у клітинах з виключеним ERN1 дефіцит глюкози зменшує експресію цього гена. Результати цього дослідження чітко продемонстрували, що рівень експресії генів PDGFC, PDGFRA та PDGFRB у клітинах гліоми лінії U87 залежить від блокади опосередкованого ERN1 стресу ендоплазматичного ретикулуму і переважно змінюється за умов дефіциту глутаміну та глюкози в залежності від функції сигнального ензиму ERN1.
Ключові слова: експресія мРНК, виключення ERN1, PDGFC, PDGFRA, PDGFRB, дефіцит глутаміну, дефіцит глюкози,клітини гліоми лінії U87.
Посилання
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Bruland O., Fluge Ø., Akslen L.A., Eiken H.G., Lillehaug J.R., Varhaug J.E., Knappskog P.M. Inverse correlation between PDGFC expression and lymphocyte infiltration in human papillary thyroid carcinomas. BMC Cancer. 2009; 9: 425.
Cheng S., Li Y., Yang Y., Feng D., Yang L., Ma Q., Zheng S., Meng R., Wang S., Wang S., Jiang W.G., He J. Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling. FEBS Lett. 2013; 587(20): 3289–3295.
Denko N.C. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nature Reviews Cancer. 2008; 8: 705–713.
Drogat B., Auguste P., Nguyen D.T., Bouchecareilh M., Pineau R., Nalbantoglu J., Kaufman R.J., 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: 6700–6707.
Fels D.R., Koumenis C. The PERK/eIF2a/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biology & Therapy. 2006; 5(7): 723–728.
Hetz C., Chevet E., Harding H.P. Targeting the unfolded protein response in disease. Nat. Rev. Drug Discov. 2013; 12(9): 703–719.
Hollien J., Lin J.H., Li H., Stevens N., Walter P., Weissman J.S. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J. Cell. Biol. 2009; 186(3): 323 – 331.
Hose D., Moreaux J., Meissner T., Seckinger A., Goldschmidt H., Benner A., Mahtouk K., Hillengass J., Rème T., De Vos J., Hundemer M., Condomines M., Bertsch U., Rossi J.F., Jauch A., Klein B., Möhler T. Induction of angiogenesis by normal and malignant plasma cells. Blood. 2009; 114(1): 128–143.
Johnson A. B., Denko N., Barton M. C. Hypoxia induces a novel signature of chromatin modifications and global repression of transcription. Mutat. Res. 2008; 640: 174 – 179.
Korennykh A.V., Egea P.F., Korostelev A.A., Finer-Moore J., Zhang C., Shokat K.M., Stroud R.M., Walter P. The unfolded protein response signals through high-order assembly of Ire1. Nature. 2009; 457(7230): 687–693.
Lee C., Zhang F., Tang Z., Liu Y., Li X. PDGF-C: a new performer in the neurovascular interplay.. Trends Mol. Med. 2013; 19(8): 474–486.
Lee J., Sun C., Zhou Y., Lee J., Gokalp D., Herrema H., Park S.W., Davis R.J., Ozcan U. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nature Medicine. 2011; 17(10): 1251–1260.
Lenihan C.R., Taylor C.T. The impact of hypoxia on cell death pathways.. Biochem. Soc. Trans. 2013; 41(2): 657–663.
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; 307(10): 901–907.
Maurel M, Chevet E, Tavernier J, Gerlo S. Getting RIDD of RNA: IRE1 in cell fate regulation.. Trends Biochem. Sci. 2014; 39(5): 245–254.
Minchenko D.O., Hubenya O.V., Terletsky B.M., Moenner M., Minchenko O.H. Effect of hypoxia, glutamine and glucose deprivation on the expression of cyclin and cyclin-dependent kinase genes in glioma cell line U87 and its subline with suppressed activity of signaling enzyme endoplasmic reticulum-nuclei-1. Ukr. Biokhim. Zh. 2011; 83(1): 18-29.
Minchenko O.H., Kharkova A.P., Bakalets T.V., Kryvdiuk I.V. Endoplasmic reticulum stress, its sensor and signaling systems and the role in the regulation of gene expressions in malignant tumor growth and hypoxia.. Ukr. Biochim. J. 2013; 85(5): 5–16.
Minchenko O.H., Kubaichuk K.I., Minchenko D.O., Kovalevska O.V., Kulinich A.O., Lypova N.M. Molecular mechanisms of ERN1-mediated angiogenesis.. Int. J. Physiol. Pathophysiol. 2014; 5(1): 1–22.
Moenner M., Pluquet O., Bouchecareilh M., Chevet E. Integrated endoplasmic reticulum stress responses in cancer.. Cancer Res. 2007; 67(22): 10631–10634.
Park S.W., Zhou Y., Lee J., Lu A., Sun C., Chung J., Ueki K., Ozcan U. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation.. Nature Medicine. 2010; 16(4): 429–437.
Pereira E.R., Liao N., Neale G.A., Hendershot L.M. Transcriptional and post-transcriptional regulation of proangiogenic factors by the unfolded protein response. // PLoS One. 2010; 5(9): e12521.
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 S.J., Taouji S., Hallett M., Sarkaria J.N., Anderson K., Wu W., Rodriguez F.J., Rosenbaum J., Saltel F., Fernandez-Zapico M.E., Chevet E. Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα. Cancer Res. 2013; 73(15): 4732–4743.
Romero-Ramirez L., Cao H., Nelson D., Hammond E., Lee A.H., Yoshida H., Mori K., Glimcher L.H., Denko N.C., Giaccia A.J., Le Q.-T., Koong A.C. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth.. Cancer Res. 2004; 64(17): 5943 – 5947.
Ruffini F., Tentori L., Dorio A.S., Arcelli D., D'Amati G., D'Atri S., Graziani G., Lacal P.M. Platelet-derived growth factor C and calpain-3 are modulators of human melanoma cell invasiveness. Oncol. Rep. 2013; 30(6): 2887–2896.
Schröder M. Endoplasmic reticulum stress responses. Cell. Mol. Life Sci. 2008; 65(6): 862–894.
Sciaccaluga M., D'Alessandro G., Pagani F., Ferrara G., Lopez N., Warr T., Gorello P., Porzia A., Mainiero F., Santoro A., Esposito V., Cantore G., Castigli E., Limatola C. Functional cross talk between CXCR4 and PDGFR on glioblastoma cells is essential for migration.. PLoS ONE. 2013; 8(9): E73426.
Son D., Na Y.R., Hwang E.S., Seok S.H. Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation. J. Biol. Chem. 2014; 289(9): 6225–6235.
Sun Y, Zhang W, Chen D, Lv Y, Zheng J, Lilljebjorn H, Ran L, Bao Z, Soneson C, Sjogren HO, Salford LG, Ji J, French PJ, Fioretos T, Jiang T and Fan X. A glioma classification scheme based on coexpression modules of EGFR and PDGFRA.. Proc. Natl. Acad. Sci. U.S.A. 2014; 111(9): 3538–3543.
Wang S., Kaufman R.J. The impact of the unfolded protein response on human disease.. J. Cell. Biol. 2012; 197(7): 857-867.
Wright J.H., Johnson M.M., Shimizu-Albergine M., Bauer R.L., Hayes B.J., Surapisitchat J., Hudkins K.L., Riehle K.J., Johnson S.C., Yeh M.M., Bammler T.K., Beyer R.P., Gilbertson D.G., Alpers C.E., Fausto N., Campbell J.S. Paracrine activation of hepatic stellate cells in platelet-derived growth factor C transgenic mice: evidence for stromal induction of hepatocellular carcinoma.. Int. J. Cancer. 2014; 134(4): 778–788.
Zhang K., Kaufman R.J. The unfolded protein response: a stress signaling pathway critical for health and disease.. Neurology. 2006; 66(2 (Suppl 1)): 102–109.
Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J., Fisher S.J., White M.F., Biddinger S.B., Ozcan U. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.. Nature Medicine. 2011; 17(3): 356–365.
Aragón T., van Anken E., Pincus D., Serafimova I.M., Korennykh A.V., Rubio C.A., Walter P. Messenger RNA targeting to endoplasmic reticulum stress signalling sites. Nature. 2009; 457(N 7230): 736–740.
Auf G., Jabouille A., Delugin M., Guérit S., Pineau R., North S., Platonova N., Maitre M., Favereaux A., Seno M., Bikfalvi A., Minchenko D., Minchenko O., Moenner M. High epiregulin expression in human U87 glioma cells relies on IRE1 and promotes autocrine growth through EGF receptor. BMC Cancer. 2013; 13(1): 597.
Auf G., Jabouille A., Guérit S., Pineau R., Delugin M., Bouchecareilh M., Favereaux A., Maitre M., Gaiser T., von Deimling A., Czabanka M., Vajkoczy P., Chevet E., Bikfalvi A., Moenner M. A shift from an angiogenic to invasive phenotype induced in malignant glioma by inhibition of the unfolded protein response sensor IRE1. Proc. Natl. Acad. Sci. U.S.A. 2010; 107(35): 1555–15558.
Bi M., Naczki C., Koritzinsky M., Fels D., Blais J., Hu N., Harding H., Novoa I., Varia M., Raleigh J., Scheuner D., Kaufman R.J., Bell J., Ron D., Wouters B.G., Koumenis C. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J. 2005; 24(19): 3470–34815.
Bruland O., Fluge Ø., Akslen L.A., Eiken H.G., Lillehaug J.R., Varhaug J.E., Knappskog P.M. Inverse correlation between PDGFC expression and lymphocyte infiltration in human papillary thyroid carcinomas. BMC Cancer. 2009; 9: 425.
Cheng S., Li Y., Yang Y., Feng D., Yang L., Ma Q., Zheng S., Meng R., Wang S., Wang S., Jiang W.G., He J. Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling. FEBS Lett. 2013; 587(20): 3289–3295.
Denko N.C. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nature Reviews Cancer. 2008; 8: 705–713.
Drogat B., Auguste P., Nguyen D.T., Bouchecareilh M., Pineau R., Nalbantoglu J., Kaufman R.J., 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: 6700–6707.
Fels D.R., Koumenis C. The PERK/eIF2a/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biology & Therapy. 2006; 5(7): 723–728.
Hetz C., Chevet E., Harding H.P. Targeting the unfolded protein response in disease. Nat. Rev. Drug Discov. 2013; 12(9): 703–719.
Hollien J., Lin J.H., Li H., Stevens N., Walter P., Weissman J.S. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J. Cell. Biol. 2009; 186(3): 323 – 331.
Hose D., Moreaux J., Meissner T., Seckinger A., Goldschmidt H., Benner A., Mahtouk K., Hillengass J., Rème T., De Vos J., Hundemer M., Condomines M., Bertsch U., Rossi J.F., Jauch A., Klein B., Möhler T. Induction of angiogenesis by normal and malignant plasma cells. Blood. 2009; 114(1): 128–143.
Johnson A. B., Denko N., Barton M. C. Hypoxia induces a novel signature of chromatin modifications and global repression of transcription. Mutat. Res. 2008; 640: 174 – 179.
Korennykh A.V., Egea P.F., Korostelev A.A., Finer-Moore J., Zhang C., Shokat K.M., Stroud R.M., Walter P. The unfolded protein response signals through high-order assembly of Ire1. Nature. 2009; 457(7230): 687–693.
Lee C., Zhang F., Tang Z., Liu Y., Li X. PDGF-C: a new performer in the neurovascular interplay.. Trends Mol. Med. 2013; 19(8): 474–486.
Lee J., Sun C., Zhou Y., Lee J., Gokalp D., Herrema H., Park S.W., Davis R.J., Ozcan U. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nature Medicine. 2011; 17(10): 1251–1260.
Lenihan C.R., Taylor C.T. The impact of hypoxia on cell death pathways.. Biochem. Soc. Trans. 2013; 41(2): 657–663.
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; 307(10): 901–907.
Maurel M, Chevet E, Tavernier J, Gerlo S. Getting RIDD of RNA: IRE1 in cell fate regulation.. Trends Biochem. Sci. 2014; 39(5): 245–254.
Minchenko D.O., Hubenya O.V., Terletsky B.M., Moenner M., Minchenko O.H. Effect of hypoxia, glutamine and glucose deprivation on the expression of cyclin and cyclin-dependent kinase genes in glioma cell line U87 and its subline with suppressed activity of signaling enzyme endoplasmic reticulum-nuclei-1. Ukr. Biokhim. Zh. 2011; 83(1): 18-29.
Minchenko O.H., Kharkova A.P., Bakalets T.V., Kryvdiuk I.V. Endoplasmic reticulum stress, its sensor and signaling systems and the role in the regulation of gene expressions in malignant tumor growth and hypoxia.. Ukr. Biochim. J. 2013; 85(5): 5–16.
Minchenko O.H., Kubaichuk K.I., Minchenko D.O., Kovalevska O.V., Kulinich A.O., Lypova N.M. Molecular mechanisms of ERN1-mediated angiogenesis.. Int. J. Physiol. Pathophysiol. 2014; 5(1): 1–22.
Moenner M., Pluquet O., Bouchecareilh M., Chevet E. Integrated endoplasmic reticulum stress responses in cancer.. Cancer Res. 2007; 67(22): 10631–10634.
Park S.W., Zhou Y., Lee J., Lu A., Sun C., Chung J., Ueki K., Ozcan U. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation.. Nature Medicine. 2010; 16(4): 429–437.
Pereira E.R., Liao N., Neale G.A., Hendershot L.M. Transcriptional and post-transcriptional regulation of proangiogenic factors by the unfolded protein response. // PLoS One. 2010; 5(9): e12521.
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 S.J., Taouji S., Hallett M., Sarkaria J.N., Anderson K., Wu W., Rodriguez F.J., Rosenbaum J., Saltel F., Fernandez-Zapico M.E., Chevet E. Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα. Cancer Res. 2013; 73(15): 4732–4743.
Romero-Ramirez L., Cao H., Nelson D., Hammond E., Lee A.H., Yoshida H., Mori K., Glimcher L.H., Denko N.C., Giaccia A.J., Le Q.-T., Koong A.C. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth.. Cancer Res. 2004; 64(17): 5943 – 5947.
Ruffini F., Tentori L., Dorio A.S., Arcelli D., D'Amati G., D'Atri S., Graziani G., Lacal P.M. Platelet-derived growth factor C and calpain-3 are modulators of human melanoma cell invasiveness. Oncol. Rep. 2013; 30(6): 2887–2896.
Schröder M. Endoplasmic reticulum stress responses. Cell. Mol. Life Sci. 2008; 65(6): 862–894.
Sciaccaluga M., D'Alessandro G., Pagani F., Ferrara G., Lopez N., Warr T., Gorello P., Porzia A., Mainiero F., Santoro A., Esposito V., Cantore G., Castigli E., Limatola C. Functional cross talk between CXCR4 and PDGFR on glioblastoma cells is essential for migration.. PLoS ONE. 2013; 8(9): E73426.
Son D., Na Y.R., Hwang E.S., Seok S.H. Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation. J. Biol. Chem. 2014; 289(9): 6225–6235.
Sun Y, Zhang W, Chen D, Lv Y, Zheng J, Lilljebjorn H, Ran L, Bao Z, Soneson C, Sjogren HO, Salford LG, Ji J, French PJ, Fioretos T, Jiang T and Fan X. A glioma classification scheme based on coexpression modules of EGFR and PDGFRA.. Proc. Natl. Acad. Sci. U.S.A. 2014; 111(9): 3538–3543.
Wang S., Kaufman R.J. The impact of the unfolded protein response on human disease.. J. Cell. Biol. 2012; 197(7): 857-867.
Wright J.H., Johnson M.M., Shimizu-Albergine M., Bauer R.L., Hayes B.J., Surapisitchat J., Hudkins K.L., Riehle K.J., Johnson S.C., Yeh M.M., Bammler T.K., Beyer R.P., Gilbertson D.G., Alpers C.E., Fausto N., Campbell J.S. Paracrine activation of hepatic stellate cells in platelet-derived growth factor C transgenic mice: evidence for stromal induction of hepatocellular carcinoma.. Int. J. Cancer. 2014; 134(4): 778–788.
Zhang K., Kaufman R.J. The unfolded protein response: a stress signaling pathway critical for health and disease.. Neurology. 2006; 66(2 (Suppl 1)): 102–109.
Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J., Fisher S.J., White M.F., Biddinger S.B., Ozcan U. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.. Nature Medicine. 2011; 17(3): 356–365.
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Опубліковано
2015-06-30
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Розділ
БІОХІМІЯ, БІОТЕХНОЛОГІЯ, МОЛЕКУЛЯРНА ГЕНЕТИКА
