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Clinical Cancer Drugs


ISSN (Print): 2212-697X
ISSN (Online): 2212-6988

Review Article

Inhibition of ERN1 Signaling is Important for the Suppression of Tumor Growth

Author(s): Oleksandr H. Minchenko*, Dariia O. Tsymbal, Olena O. Khita and Dmytro O. Minchenko

Volume 8, Issue 1, 2021

Published on: 06 October, 2021

Article ID: e061021197026 Pages: 12

DOI: 10.2174/2212697X08666211006100250

Price: $65


Background: Endoplasmic reticulum to nucleus signaling 1 (ERN1) is a major signaling pathway of endoplasmic reticulum stress and is crucial for malignant tumor growth.

Objective: The article aims to discuss the recent progress in the discovery of endoplasmic reticulum stress targets and their involvement in tumor growth.

Methods: Literature from the PubMed database related to the endoplasmic reticulum stress involvement in the tumor growth and chemoresistance was searched and reviewed.

Results: The endoplasmic reticulum stress plays an important part in malignant tumor growth and is involved in invasion and metastasis. Inhibition of protein kinase and endoribonuclease activities of the ERN1 signaling protein significantly reduces tumor growth through down-regulation of angiogenesis and cell proliferation but activates the invasion. ERN1 knockdown affects the expression of many genes associated with the regulation of apoptosis, cell proliferation, and survival as well as reprograms the hypoxic regulation of most gene expressions. Simultaneously, inhibition of ERN1 endoribonuclease only has a stronger suppressive effect on tumor growth and decreases the invasiveness.

Conclusion: Present review summarizes the recent advances in inhibiting ERN1 signaling that regulates tumor growth. Further understanding of the regulatory mechanisms of genome reprogramming upon inhibition of ERN1 signaling may help discover new possibilities for developing novel effective therapeutics.

Keywords: Tumor growth, cell proliferation, ERN1 inhibition, ERN1 endoribonuclease signaling, ERN1 protein kinase, U87glioma cells.

Graphical Abstract
Bravo R, Parra V, Gatica D, et al. Endoplasmic reticulum and the unfolded protein response: Dynamics and metabolic integration. Int Rev Cell Mol Biol 2013; 301: 215-90.
[] [PMID: 23317820]
Kaufman RJ, Back SH, Song B, Han J, Hassler J. The unfolded protein response is required to maintain the integrity of the endoplasmic reticulum, prevent oxidative stress and preserve differentiation in β-cells. Diabetes Obes Metab 2010; 12(Suppl. 2): 99-107.
[] [PMID: 21029306]
Schröder M. Endoplasmic reticulum stress responses. Cell Mol Life Sci 2008; 65(6): 862-94.
[] [PMID: 18038217]
Doultsinos D, Avril T, Lhomond S, Dejeans N, Guédat P, Chevet E. Control of the unfolded protein response in health and disease. SLAS Discov 2017; 22(7): 787-800.
[] [PMID: 28453376]
Hetz C, Zhang K, Kaufman RJ. Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol Cell Biol 2020; 21(8): 421-38.
[] [PMID: 32457508]
Moenner M, Pluquet O, Bouchecareilh M, Chevet E. Integrated endoplasmic reticulum stress responses in cancer. Cancer Res 2007; 67(22): 10631-4.
[] [PMID: 18006802]
Obacz J, Avril T, Le Reste PJ, et al. Endoplasmic reticulum proteostasis in glioblastoma-from molecular mechanisms to therapeutic perspectives. Sci Signal 2017; 10(470): eaal2323.
[] [PMID: 28292956]
Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007; 8(7): 519-29.
[] [PMID: 17565364]
Marciniak SJ. Endoplasmic reticulum stress: A key player in human disease. FEBS J 2019; 286(2): 228-31.
[] [PMID: 30677245]
Woehlbier U, Hetz C. Modulating stress responses by the UPRosome: A matter of life and death. Trends Biochem Sci 2011; 36(6): 329-37.
[] [PMID: 21482118]
Drogat B, Auguste P, Nguyen DT, et al. 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(14): 6700-7.
[] [PMID: 17638880]
Hiss DC, Gabriels GA. Implications of endoplasmic reticulum stress, the unfolded protein response and apoptosis for molecular cancer therapy. Part II: Targeting cell cycle events, caspases, NF-κB and the proteasome. Expert Opin Drug Discov 2009; 4(9): 907-21.
[] [PMID: 23480539]
Higa A, Taouji S, Lhomond S, et al. Endoplasmic reticulum stress-activated transcription factor ATF6α requires the disulfide isomerase PDIA5 to modulate chemoresistance. Mol Cell Biol 2014; 34(10): 1839-49.
[] [PMID: 24636989]
Avril T, Vauléon E, Chevet E. Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers. Oncogenesis 2017; 6(8): e373.
[] [PMID: 28846078]
Logue SE, McGrath EP, Cleary P, et al. Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy. Nat Commun 2018; 9(1): 3267.
[] [PMID: 30111846]
Harris PS, Venkataraman S, Alimova I, et al. Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells. BMC Cancer 2012; 12: 80.
[] [PMID: 22390279]
Yuzefovych LV, Musiyenko SI, Wilson GL, Rachek LI. Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS One 2013; 8(1): e54059.
[] [PMID: 23342074]
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): C901-7.
[] [PMID: 25186011]
Lee SK, Kim YS. Phosphorylation of eIF2α attenuates statin-induced apoptosis by inhibiting the stabilization and translocation of p53 to the mitochondria. Int J Oncol 2013; 42(3): 810-6.
[] [PMID: 23354132]
Auf G, Jabouille A, Guérit S, et al. Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci USA 2010; 107(35): 15553-8.
[] [PMID: 20702765]
Amin-Wetzel N, Saunders RA, Kamphuis MJ, et al. A j-protein co-chaperone recruits bip to monomerize ire1 and repress the unfolded protein response. Cell 2017; 171(7): 1625-1637.e13.
[] [PMID: 29198525]
Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2000; 2(6): 326-32.
[] [PMID: 10854322]
López I, Tournillon AS, Prado Martins R, et al. p53-mediated suppression of BiP triggers BIK-induced apoptosis during prolonged endoplasmic reticulum stress. Cell Death Differ 2017; 24(10): 1717-29.
[] [PMID: 28622297]
Kang JM, Park S, Kim SJ, et al. KIAA1324 suppresses gastric cancer progression by inhibiting the oncoprotein GRP78. Cancer Res 2015; 75(15): 3087-97.
[] [PMID: 26045166]
Yin Y, Chen C, Chen J, et al. Cell surface GRP78 facilitates hepatoma cells proliferation and migration by activating IGF-IR. Cell Signal 2017; 35: 154-62.
[] [PMID: 28389416]
Luo C, Qiu J. miR-181a inhibits cervical cancer development via downregulating GRP78. Oncol Res 2017; 25(8): 1341-8.
[] [PMID: 28245171]
Shen X, Zhang K, Kaufman RJ. The unfolded protein response-a stress signaling pathway of the endoplasmic reticulum. J Chem Neuroanat 2004; 28(1-2): 79-92.
[] [PMID: 15363493]
Hetz C, Chevet E, Oakes SA. Proteostasis control by the unfolded protein response. Nat Cell Biol 2015; 17(7): 829-38.
[] [PMID: 26123108]
Lee AH, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 2003; 23(21): 7448-59.
[] [PMID: 14559994]
Acosta-Alvear D, Zhou Y, Blais A, et al. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell 2007; 27(1): 53-66.
[] [PMID: 17612490]
Lee J, Sun C, Zhou Y, et al. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat Med 2011; 17(10): 1251-60.
[] [PMID: 21892182]
Park SW, Zhou Y, Lee J, et al. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nat Med 2010; 16(4): 429-37.
[] [PMID: 20348926]
Zhou Y, Lee J, Reno CM, et al. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nat Med 2011; 17(3): 356-65.
[] [PMID: 21317886]
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(3): 323-31.
[] [PMID: 19651891]
Aragón T, van Anken E, Pincus D, et al. Messenger RNA targeting to endoplasmic reticulum stress signalling sites. Nature 2009; 457(7230): 736-40.
[] [PMID: 19079237]
Maurel M, Chevet E, Tavernier J, Gerlo S. Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem Sci 2014; 39(5): 245-54.
[] [PMID: 24657016]
Pluquet O, Dejeans N, Bouchecareilh M, et al. Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα. Cancer Res 2013; 73(15): 4732-43.
[] [PMID: 23752693]
Oikawa D, Tokuda M, Iwawaki T. Site-specific cleavage of CD59 mRNA by endoplasmic reticulum-localized ribonuclease, IRE1. Biochem Biophys Res Commun 2007; 360(1): 122-7.
[] [PMID: 17585877]
Han D, Upton JP, Hagen A, Callahan J, Oakes SA, Papa FR. A kinase inhibitor activates the IRE1alpha RNase to confer cytoprotection against ER stress. Biochem Biophys Res Commun 2008; 365(4): 777-83.
[] [PMID: 18035051]
Han D, Lerner AG, Vande Walle L, et al. IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 2009; 138(3): 562-75.
[] [PMID: 19665977]
Backer MV, Backer JM, Chinnaiyan P. Targeting the unfolded protein response in cancer therapy. Methods Enzymol 2011; 491: 37-56.
[] [PMID: 21329793]
Almanza A, Carlesso A, Chintha C, et al. Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications. FEBS J 2019; 286(2): 241-78.
[] [PMID: 30027602]
Bouchecareilh M, Higa A, Fribourg S, Moenner M, Chevet E. Peptides derived from the bifunctional kinase/RNase enzyme IRE1α modulate IRE1α activity and protect cells from endoplasmic reticulum stress. FASEB J 2011; 25(9): 3115-29.
[] [PMID: 21680894]
Ojha R, Amaravadi RK. Targeting the unfolded protein response in cancer. Pharmacol Res 2017; 120: 258-66.
[] [PMID: 28396092]
Wang M, Law ME, Castellano RK, Law BK. The unfolded protein response as a target for anticancer therapeutics. Crit Rev Oncol Hematol 2018; 127: 66-79.
[] [PMID: 29891114]
Meng J, Liu K, Shao Y, et al. ID1 confers cancer cell chemoresistance through STAT3/ATF6-mediated induction of autophagy. Cell Death Dis 2020; 11(2): 137.
[] [PMID: 32080166]
Yarapureddy S, Abril J, Foote J, et al. ATF6α activation enhances survival against chemotherapy and serves as a prognostic indicator in osteosarcoma. Neoplasia 2019; 21(6): 516-32.
[] [PMID: 31029032]
Alasiri G, Jiramongkol Y, Zona S, et al. Regulation of PERK expression by FOXO3: A vulnerability of drug-resistant cancer cells. Oncogene 2019; 38(36): 6382-98.
[] [PMID: 31312024]
Hughes D, Mallucci GR. The unfolded protein response in neurodegenerative disorders - therapeutic modulation of the PERK pathway. FEBS J 2019; 286(2): 342-55.
[] [PMID: 29476642]
Hughes DT, Halliday M, Smith HL, et al. Targeting the kinase insert loop of PERK selectively modulates PERK signaling without systemic toxicity in mice. Sci Signal 2020; 13(644): eabb4749.
[] [PMID: 32788341]
Shi Z, Yu X, Yuan M, et al. Activation of the PERK-ATF4 pathway promotes chemo-resistance in colon cancer cells. Sci Rep 2019; 9(1): 3210.
[] [PMID: 30824833]
Salaroglio IC, Panada E, Moiso E, et al. PERK induces resistance to cell death elicited by endoplasmic reticulum stress and chemotherapy. Mol Cancer 2017; 16(1): 91.
[] [PMID: 28499449]
Auf G, Jabouille A, Delugin M, et al. High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor. BMC Cancer 2013; 13: 597.
[] [PMID: 24330607]
Lhomond S, Avril T, Dejeans N, et al. Dual IRE1 RNase functions dictate glioblastoma development. EMBO Mol Med 2018; 10(3): e7929.
[] [PMID: 29311133]
Cross BCS, Bond PJ, Sadowski PG, et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci USA 2012; 109(15): E869-78.
[] [PMID: 22315414]
Mimura N, Fulciniti M, Gorgun G, et al. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood 2012; 119(24): 5772-81.
[] [PMID: 22538852]
Ri M, Tashiro E, Oikawa D, et al. Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. Blood Cancer J 2012; 2(7): e79.
[] [PMID: 22852048]
Hetz C, Axten JM, Patterson JB. Pharmacological targeting of the unfolded protein response for disease intervention. Nat Chem Biol 2019; 15(8): 764-75.
[] [PMID: 31320759]
Stewart C, Estrada A, Kim P, et al. Regulation of IRE1α by the small molecule inhibitor 4μ8c in hepatoma cells. Endoplasmic Reticulum Stress Dis 2017; 4(1): 1-10.
[] [PMID: 29098149]
Martelli AM, Paganelli F, Chiarini F, Evangelisti C, McCubrey JA. The unfolded protein response: A novel therapeutic target in acute leukemias. Cancers (Basel) 2020; 12(2): 333.
[] [PMID: 32024211]
Sun H, Lin DC, Guo X, et al. Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemia. Oncotarget 2016; 7(14): 18736-49.
[] [PMID: 26934650]
Papandreou I, Denko NC, Olson M, et al. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood 2011; 117(4): 1311-4.
[] [PMID: 21081713]
Slabáková E, Culig Z, Remšík J, Souček K. Alternative mechanisms of miR-34a regulation in cancer. Cell Death Dis 2017; 8(10): e3100.
[] [PMID: 29022903]
Thorpe JA, Schwarze SR. IRE1alpha controls cyclin A1 expression and promotes cell proliferation through XBP-1. Cell Stress Chaperones 2010; 15(5): 497-508.
[] [PMID: 20013084]
Minchenko DO, Kharkova AP, Hubenia OV, Minchenko OH. Insulin receptor, IRS1, IRS2, INSIG1, INSIG2, RRAD, and BAIAP2 gene expressions in glioma U87 cells with ERN1 loss of function: Effect of hypoxia and glutamine or glucose deprivation. Endocr Regul 2013; 47(1): 15-26.
[] [PMID: 23363253]
Minchenko DO, Hubenya OV, Terletsky BM, Moenner M, Minchenko OH. Effect of glutamine or 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 of endoplasmic reticulum-nuclei-1. Ukr Biokhim Zh 2011; 83(1): 18-29.
[PMID: 21800645]
Minchenko OH, Luzina OY, Hnatiuk OS, Minchenko DO, Garmash YA, Ratushna OO. Expression of tumor growth related genes in IRE1 knockdown U87 glioma cells: Effect of hypoxia. Ukr Biochem J 2017; 89(5): 40-51.
Minchenko OH, Kryvdiuk IV, Minchenko DO, Riabovol OO, Halkin OV. Inhibition of IRE1 signaling affects expression of a subset genes encoding for TNF-related factors and receptors and modifies their hypoxic regulation in U87 glioma cells. Endoplasmic Reticulum Stress Dis 2016; 3(1): 1-15.
Minchenko OH, Riabovol OO, Tsymbal DO, Minchenko DO, Ratushna OO. Effect of hypoxia on the expression of nuclear genes encoding mitochondrial proteins in U87 glioma cells. Ukr Biochem J 2016; 88(3): 54-65.
[] [PMID: 29235326]
Minchenko DO, Riabovol OO, Tsymbal DO, Ratushna OO, Minchenko OH. Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells. Endocr Regul 2016; 50(3): 127-36.
[] [PMID: 27560795]
Minchenko OH, Tsymbal DO, Minchenko DO, Kovalevska OV, Karbovskyi LL, Bikfalvi A. Inhibition of ERN1 signaling enzyme affects hypoxic regulation of the expression of E2F8, EPAS1, HOXC6, ATF3, TBX3 and FOXF1 genes in U87 glioma cells. Ukr Biochem J 2015; 87(2): 76-87.
[] [PMID: 26255341]
Minchenko OH, Tsymbal DO, Minchenko DO, Riabovol OO, Halkin OV, Ratushna OO. IRE-1α regulates expression of ubiquitin specific peptidases during hypoxic response in U87 glioma cells. Endoplasmic Reticulum Stress Dis 2016; 3: 50-62.
Minchenko OH, Kryvdiuk IV, Riabovol OO, Minchenko DO, Danilovskyi SV, Ratushna OO. Inhibition of IRE1 modifies the hypoxic regulation of GADD family gene expressions in U87 glioma cells. Ukr Biochem J 2016; 88(2): 25-34.
[] [PMID: 29227599]
Minchenko DO, Kharkova AP, Halkin OV, Karbovskyi LL, Minchenko OH. Effect of hypoxia on the expression of genes encoding insulin-like growth factors and some related proteins in U87 glioma cells without IRE1 function. Endocr Regul 2016; 50(2): 43-54.
[] [PMID: 27560636]
Weil D, Hollien J. Cytoplasmic organelles on the road to mRNA decay. Biochim Biophys Acta 2013; 1829(6-7): 725-31.
[] [PMID: 23337852]
Bae D, Moore KA, Mella JM, Hayashi SY, Hollien J. Degradation of Blos1 mRNA by IRE1 repositions lysosomes and protects cells from stress. J Cell Biol 2019; 218(4): 1118-27.
[] [PMID: 30787040]
McMahon M, Samali A, Chevet E. Regulation of the unfolded protein response by noncoding RNA. Am J Physiol Cell Physiol 2017; 313(3): C243-54.
[] [PMID: 28637678]
Minchenko OH, Tsymbal DO, Moenner M, Minchenko DO, Kovalevska OV, Lypova NM. Inhibition of the endoribonuclease of ERN1 signaling enzyme affects the expression of proliferation-related genes in U87 glioma cells. Endoplasmic Reticulum Stress Dis 2015; 2(1): 18-29.
Danilovskyi SV, Minchenko DO, Moliavko OS, Kovalevska OV, Karbovskyi LL, Minchenko OH. ERN1 knockdown modifies the hypoxic regulation of TP53, MDM2, USP7 and PERP gene expressions in U87 glioma cells. Ukr Biochem J 2014; 86(4): 90-102.
[] [PMID: 25509187]
Minchenko DO, Tsymbal DO, Riabovol OO, et al. Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells. Endocr Regul 2019; 53(4): 250-62.
[] [PMID: 31734650]
Minchenko DO, Kharkova AP, Karbovskyi LL, Minchenko OH. Expression of insulin-like growth factor binding protein genes and its hypoxic regulation in U87 glioma cells depends on ERN1 mediated signaling pathway of endoplasmic reticulum stress. Endocr Regul 2015; 49(2): 73-83.
[] [PMID: 25960008]
Minchenko DO, Khita OO, Tsymbal DO, et al. Expression of IDE and PITRM1 genes in ERN1 knockdown U87 glioma cells: Effect of hypoxia and glucose deprivation. Endocr Regul 2020; 54(3): 183-95.
[] [PMID: 32857715]
Hiss DC, Gabriels GA. Implications of endoplasmic reticulum stress, the unfolded protein response and apoptosis for molecular cancer therapy. Part I: Targeting p53, Mdm2, GADD153/CHOP, GRP78/BiP and heat shock proteins. Expert Opin Drug Discov 2009; 4(8): 799-821.
[] [PMID: 23496268]
Prasad M, Pawlak KJ, Burak WE, et al. Mitochondrial metabolic regulation by GRP78. Sci Adv 2017; 3(2): e1602038.
[] [PMID: 28275724]
Urra H, Dufey E, Avril T, Chevet E, Hetz C. Endoplasmic reticulum stress and the hallmarks of cancer. Trends Cancer 2016; 2(5): 252-62.
[] [PMID: 28741511]
Ogawa H, Kaira K, Takahashi K, et al. Prognostic role of BiP/GRP78 expression as ER stress in patients with gastric adenocarcinoma. Cancer Biomark 2017; 20(3): 273-81.
[] [PMID: 28854502]
Tsai YL, Ha DP, Zhao H, et al. Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell surface where GRP78/CD109 blocks TGF-β signaling. Proc Natl Acad Sci USA 2018; 115(18): E4245-54.
[] [PMID: 29654145]
Lin J, Chung S, Ueda K, Matsuda K, Nakamura Y, Park JH. GALNT6 stabilizes grp78 protein by o-glycosylation and enhances its activity to suppress apoptosis under stress condition. Neoplasia 2017; 19(1): 43-53.
[] [PMID: 28110670]
Sun C, Han C, Jiang Y, et al. Inhibition of GRP78 abrogates radioresistance in oropharyngeal carcinoma cells after EGFR inhibition by cetuximab. PLoS One 2017; 12(12): e0188932.
[] [PMID: 29232380]
Zhao H, Tang W, Chen X, et al. The NAMPT/E2F2/SIRT1 axis promotes proliferation and inhibits p53-dependent apoptosis in human melanoma cells. Biochem Biophys Res Commun 2017; 493(1): 77-84.
[] [PMID: 28919418]
Alaee M, Khaghani S, Behroozfar K, Hesari Z, Ghorbanhosseini SS, Nourbakhsh M. Inhibition of nicotinamide phosphoribosyltransferase induces apoptosis in estrogen receptor-positive MCF-7 breast cancer cells. J Breast Cancer 2017; 20(1): 20-6.
[] [PMID: 28382091]
Xu R, Yuan Z, Yang L, Li L, Li D, Lv C. Inhibition of NAMPT decreases cell growth and enhances susceptibility to oxidative stress. Oncol Rep 2017; 38(3): 1767-73.
[] [PMID: 28714034]
Thakur BK, Lippka Y, Dittrich T, Chandra P, Skokowa J, Welte K. NAMPT pathway is involved in the FOXO3a-mediated regulation of GADD45A expression. Biochem Biophys Res Commun 2012; 420(4): 714-20.
[] [PMID: 22430142]
Tsitsipatis D, Grammatikakis I, Driscoll RK, et al. AUF1 ligand circPCNX reduces cell proliferation by competing with p21 mRNA to increase p21 production. Nucleic Acids Res 2021; 49(3): 1631-46.
[] [PMID: 33444453]
Galli U, Colombo G, Travelli C, Tron GC, Genazzani AA, Grolla AA. Recent advances in NAMPT inhibitors: A novel immunotherapic strategy. Front Pharmacol 2020; 11: 656.
[] [PMID: 32477131]
Lucena-Cacace A, Otero-Albiol D, Jiménez-García MP, Muñoz- Galvan S, Carnero A. NAMPT Is a potent oncogene in colon cancer progression that modulates cancer stem cell properties and resistance to therapy through Sirt1 and PARP. Clin Cancer Res 2018; 24(5): 1202-15.
[] [PMID: 29203587]
Yan X, Zhao J, Zhang R. Visfatin mediates doxorubicin resistance in human colorectal cancer cells via up regulation of multidrug resistance 1 (MDR1). Cancer Chemother Pharmacol 2017; 80(2): 395-403.
[] [PMID: 28667355]
Tsymbal DO, Minchenko DO, Luzina OY, Riabovol OO, Danilovskyi SV, Minchenko OH. Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells. Endocr Regul 2020; 54(1): 31-42.
[] [PMID: 32597148]
Bong IP, Ng CC, Fakiruddin SK, Lim MN, Zakaria Z. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study. Bosn J Basic Med Sci 2016; 16(4): 268-75.
[PMID: 27754828]
Fritz JM, Dong M, Apsley KS, et al. Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum stress and metabolic defects. Mol Biol Cell 2014; 25(4): 431-40.
[] [PMID: 24336520]
Carreras-Sureda A, Jaña F, Urra H, et al. Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics. Nat Cell Biol 2019; 21(6): 755-67.
[] [PMID: 31110288]
Feng J, Yan PF, Zhao HY, Zhang FC, Zhao WH, Feng M. Inhibitor of nicotinamide phosphoribosyltransferase sensitizes glioblastoma cells to temozolomide via Activating ROS/JNK Signaling Pathway. BioMed Res Int 2016; 2016: 1450843.
[] [PMID: 28097126]

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