Integrated stress response is critical for gemcitabine resistance in pancreatic ductal adenocarcinoma

Cell Death and Disease

Volumn 6, Issue 10, 2015, Pages

  Palam, L R ^a   Gore, J ^a   Craven, K E ^a   Wilson, J L ^a   Korc, M ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; BCL2 RELATED PROTEIN A1; BEX2 PROTEIN; GEMCITABINE; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 34; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45; INITIATION FACTOR 2; MESSENGER RNA; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NUPR1 PROTEIN; PEPTIDES AND PROTEINS; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG; 2-(4-CHLOROPHENOXY)-N-(4-(2-(4-CHLOROPHENOXY)ACETAMIDO)CYCLOHEXYL)ACETAMIDE; ACETAMIDE DERIVATIVE; ANTINEOPLASTIC ANTIMETABOLITE; ATF4 PROTEIN, HUMAN; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; CYCLOHEXYLAMINE DERIVATIVE; DEOXYCYTIDINE; P8 PROTEIN, HUMAN; PHOSPHOPROTEIN PHOSPHATASE 1; PPP1R15A PROTEIN, HUMAN; TRANSCRIPTOME; TUMOR PROTEIN;

5' UNTRANSLATED REGION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CANCER RESISTANCE; CANCER SIZE; CHEMOSENSITIVITY; CONTROLLED STUDY; FIBROBLAST; INTEGRATED STRESS RESPONSE; LUCIFERASE ASSAY; MOUSE; NONHUMAN; PANCREAS ADENOCARCINOMA; PANCREATIC CANCER CELL LINE; POLYSOME; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RNA SEQUENCE; RNA TRANSLATION; STRESS; UPREGULATION; ANALOGS AND DERIVATIVES; ANIMAL; CARCINOMA, PANCREATIC DUCTAL; DRUG RESISTANCE; DRUG SCREENING; GENE EXPRESSION; GENETICS; HUMAN; METABOLISM; NUDE MOUSE; OXIDATIVE STRESS; PANCREATIC NEOPLASMS; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ACETAMIDES; ACTIVATING TRANSCRIPTION FACTOR 4; ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CYCLOHEXYLAMINES; DEOXYCYTIDINE; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION; HUMANS; MICE, NUDE; NEOPLASM PROTEINS; OXIDATIVE STRESS; PANCREATIC NEOPLASMS; PROTEIN BIOSYNTHESIS; PROTEIN PHOSPHATASE 1; SIGNAL TRANSDUCTION; TRANSCRIPTOME; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84962335303     PISSN: None     EISSN: 20414889     Source Type: Journal    
DOI: 10.1038/cddis.2015.264     Document Type: Article

References (65)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64:9-29.
2. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369: 1691-1703.
3. Wek RC, Jiang HY, Anthony TG. Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 2006; 34(Pt 1): 7-11.
4. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 2011; 334: 1081-1086.
5. Han A, Yu C, Lu L, Fujiwara Y, Browne C, Chin G et al. Heme-regulated eIF2α kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. EMBO J 2001; 20: 6909-6918.
6. Garcia MA, Meurs EF, Esteban M. The dsRNA protein kinase PKR: virus and cell control. Biochimie 2007; 89: 799-811.
7. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell 2000; 6: 1099-1108.
8. Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 2003; 11: 619-633.
9. Lu PD, Jousse C, Marciniak SJ, Zhang Y, Novoa I, Scheuner D et al. Cytoprotection by preemptive conditional phosphorylation of translation initiation factor 2. EMBO J 2004; 23: 169-179.
10. Marciniak SJ, Ron D. Endoplasmic reticulum stress signaling in disease. Physiol Rev 2006; 86: 1133-1149.
11. Ottenhof NA, de Wilde RF, Maitra A, Hruban RH, Offerhaus GJA. Molecular characteristics of pancreatic ductal adenocarcinoma. Patholog Res Int 2011; 2011: 620601.
12. McCleary-Wheeler AL, McWilliams R, Fernandez-Zapico ME. Aberrant signaling pathways in pancreatic cancer: a two compartment view. Mol Carcinog 2012; 51: 25-39.
13. Wang Z, Li Y, Ahmad A, Banerjee S, Azmi AS, Kong D et al. Pancreatic cancer: understanding and overcoming chemoresistance. Nat Rev Gastroenterol Hepatol 2011; 8: 27-33.
14. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med 2014; 371: 1039-1049.
15. Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev 2011; 25: 717-729.
16. Kang R, Tang D. Autophagy in pancreatic cancer pathogenesis and treatment. Am J Cancer Res 2012; 2: 383-396.
17. Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G et al. EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell 2013; 154: 1269-1284.
18. Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, Hu N et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J 2005; 24: 3470-3481.
19. Ye J, Kumanova M, Hart LS, Sloane K, Zhang H, De Panis DN et al. The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J 2010; 29: 2082-2096.
20. Ju HQ, Gocho T, Aguilar M, Wu M, Zhuang ZN, Fu J et al. Mechanisms of overcoming intrinsic resistance to gemcitabine in pancreatic ductal adenocarcinoma through the redox modulation. Mol Cancer Ther 2014; 14: 788-798.
21. Donadelli M, Dando I, Zaniboni T, Costanzo C, Dalla Pozza E, Scupoli MT et al. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis 2011; 2: e152.
22. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. eLife 2013; 2: e00498.
23. Brush MH, Weiser DC, Shenolikar S. Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol Cell Biol 2003; 23: 1292-1303.
24. Hinnebusch AG. Translational regulation of GCN4 and the general amino acid control of yeast. Annu Rev Microbiol 2005; 59: 407-450.
25. Vattem KM, Wek RC. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc Natl Acad Sci USA 2004; 101: 11269-11274.
26. Han J, Back SH, Hur J, Lin YH, Gildersleeve R, Shan J et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol 2013; 15: 481-490.
27. Matzuk MM, Finegold MJ, Mather JP, Krummen L, Lu H, Bradley A. Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc Natl Acad Sci USA 1994; 91: 8817-8821.
28. Bhowmick R, Girotti AW. Pro-survival and pro-growth effects of stress-induced nitric oxide in a prostate cancer photodynamic therapy model. Cancer Lett 2014; 343: 115-122.
29. Watanabe N, Wachi S, Fujita T. Identification and characterization of BCL-3-binding protein: implications for transcription and DNA repair or recombination. J Biol Chem 2003; 278: 26102-26110.
30. Koussounadis A, Langdon SP, Harrison DJ, Smith VA. Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian cancer. Br J Cancer 2014; 110: 2975-2984.
31. Grasso D, Garcia MN, Hamidi T, Cano C, Calvo E, Lomberk G et al. Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating Kras(G12D)-induced senescence. Cell Death Differ 2014; 21: 1633-1641.
32. Cano CE, Hamidi T, Garcia MN, Grasso D, Loncle C, Garcia S et al. Genetic inactivation of Nupr1 acts as a dominant suppressor event in a two-hit model of pancreatic carcinogenesis. Gut 2014; 63: 984-995.
33. Hamidi T, Algul H, Cano CE, Sandi MJ, Molejon MI, Riemann M et al. Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis. J Clin Invest 2012; 122: 2092-2103.
34. Averous J, Lambert-Langlais S, Cherasse Y, Carraro V, Parry L, B'Chir W et al. Amino acid deprivation regulates the stress-inducible gene p8 via the GCN2/ATF4 pathway. Biochem Biophys Res Commun 2011; 413: 24-29.
35. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674.
36. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-1806.
37. Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012; 491: 399-405.
38. Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015; 518: 495-501.
39. Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE et al. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol 2011; 29: 4548-4554.
40. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-1825.
41. Chu GC, Kimmelman AC, Hezel AF, DePinho RA. Stromal biology of pancreatic cancer. J Cell Biochem 2007; 101: 887-907.
42. Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 2007; 6: 1186-1197.
43. Hung SW, Mody HR, Govindarajan R. Overcoming nucleoside analog chemoresistance of pancreatic cancer: a therapeutic challenge. Cancer Lett 2012; 320: 138-149.
44. Liu F, Gore AJ, Wilson JL, Korc M. DUSP1 is a novel target for enhancing pancreatic cancer cell sensitivity to gemcitabine. PloS One 2014; 9: e84982.
45. Liau SS, Whang E. HMGA1 is a molecular determinant of chemoresistance to gemcitabine in pancreatic adenocarcinoma. Clin Cancer Res 2008; 14: 1470-1477.
46. Nath S, Daneshvar K, Roy LD, Grover P, Kidiyoor A, Mosley L et al. MUC1 induces drug resistance in pancreatic cancer cells via upregulation of multidrug resistance genes. Oncogenesis 2013; 2: e51.
47. Skrypek N, Duchene B, Hebbar M, Leteurtre E, van Seuningen I, Jonckheere N. The MUC4 mucin mediates gemcitabine resistance of human pancreatic cancer cells via the Concentrative Nucleoside Transporter family. Oncogene 2013; 32: 1714-1723.
48. Bafna S, Kaur S, Momi N, Batra SK. Pancreatic cancer cells resistance to gemcitabine: the role of MUC4 mucin. Br J Cancer 2009; 101: 1155-1161.
49. Arora S, Bhardwaj A, Singh S, Srivastava SK, McClellan S, Nirodi CS et al. An undesired effect of chemotherapy: gemcitabine promotes pancreatic cancer cell invasiveness through reactive oxygen species-dependent, nuclear factor kappaB- and hypoxiainducible factor 1alpha-mediated up-regulation of CXCR4. J Biol Chem 2013; 288: 21197-21207.
50. Sidrauski C, McGeachy AM, Ingolia NT, Walter P. The small molecule ISRIB reverses the effects of eIF2alpha phosphorylation on translation and stress granule assembly. eLife 2015; 4: e05033.
51. Buchan JR, Parker R. Eukaryotic stress granules: the ins and outs of translation. Mol Cell 2009; 36: 932-941.
52. Sekine Y, Zyryanova A, Crespillo-Casado A, Fischer PM, Harding HP, Ron D. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science 2015; 348: 1027-1030.
53. Naderi A, Liu J, Bennett IC. BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer. Int J Cancer 2010; 126: 1596-1610.
54. Naderi A, Teschendorff AE, Beigel J, Cariati M, Ellis IO, Brenton JD et al. BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/ nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines. Cancer Res 2007; 67: 6725-6736.
55. Vogler M. BCL2A1: the underdog in the BCL2 family. Cell Death Differ 2012; 19: 67-74.
56. Rooswinkel RW, van de Kooij B, Verheij M, Borst J. Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B. Cell Death Dis 2012; 3: e366.
57. Atkins C, Liu Q, Minthorn E, Zhang SY, Figueroa DJ, Moss K et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 2013; 73: 1993-2002.
58. Clarke HJ, Chambers JE, Liniker E, Marciniak SJ. Endoplasmic reticulum stress in malignancy. Cancer Cell 2014; 25: 563-573.
59. Halliday M, Radford H, Sekine Y, Moreno J, Verity N, le Quesne J et al. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis 2015; 6: e1672.
60. Palam LR, Baird TD, Wek RC. Phosphorylation of eIF2 facilitates ribosomal bypass of an inhibitory upstream ORF to enhance CHOP translation. J Biol Chem 2011; 286: 10939-10949.
61. Norris AM, Gore A, Balboni A, Young A, Longnecker DS, Korc M. AGR2 is a SMAD4-suppressible gene that modulates MUC1 levels and promotes the initiation and progression of pancreatic intraepithelial neoplasia. Oncogene 2013; 32: 3867-3876.
62. Jonckheere N, Skrypek N, Van Seuningen I. Mucins and tumor resistance to chemotherapeutic drugs. Biochim Biophys Acta 2014; 1846: 142-151.
63. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol 2010; 11: R106.
64. Gregory R, Warnes BB, Bonebakker L, Gentleman R, Andy Liaw WH, Lumley T et al. Various R programming tools for plotting data. R package version 2.14.2, 2014.
65. Gore AJ, Deitz SL, Palam LR, Craven KE, Korc M. Pancreatic cancer-associated retinoblastoma 1 dysfunction enables TGF-beta to promote proliferation. J Clin Invest 2014; 124: 338-352.