HuR contributes to TRAIL resistance by restricting death receptor 4 expression in pancreatic cancer cells

Molecular Cancer Research

Volumn 14, Issue 7, 2016, Pages 599-611

  Romeo, Carmella ^a   Weber, Matthew C ^a   Zarei, Mahsa ^a   DeCicco, Danielle ^a   Chand, Saswati N ^a   Lobo, Angie D ^a   Winter, Jordan M ^a   Sawicki, Janet A ^b   Sachs, Jonathan N ^c   Meisner Kober, Nicole ^d   Yeo, Charles J ^a   Vadigepalli, Rajanikanth ^a   Tykocinski, Mark L ^a   Brody, Jonathan R ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b LANKENAU INSTITUTE FOR MEDICAL RESEARCH   (United States)

^c University of Minnesota   (United States)

^d Novartis Institutes for BioMedical Research   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TUBULIN; ANTINEOPLASTIC AGENT; CALVASCULIN; CASPASE 3; CASPASE 8; CYCLIN DEPENDENT KINASE 6; CYCLINE; DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEIN; DEATH RECEPTOR 4; DEATH RECEPTOR 5; ELAV LIKE PROTEIN 1; GEMCITABINE; INTERLEUKIN 8; MESSENGER RNA; MS 444; PROTEIN BCL 2; PROTEIN C JUN; PROTEIN FOS; PROTEIN KINASE B BETA; PROTEIN MCL 1; PROTEIN P53; TRANSCRIPTION FACTOR E2F3; TRANSCRIPTION FACTOR JUNB; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND RECEPTOR; UNCLASSIFIED DRUG; ELAVL1 PROTEIN, HUMAN; RECOMBINANT PROTEIN; TNFRSF10A PROTEIN, HUMAN; TNFSF10 PROTEIN, HUMAN;

3' UNTRANSLATED REGION; APOPTOSIS; ARTICLE; AU RICH ELEMENT; CELL NUCLEUS; CELL PROLIFERATION; CELL SURFACE; CELL VIABILITY; CONTROLLED STUDY; CYTOPLASM; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IC50; PANCREAS ADENOCARCINOMA; PANCREATIC CANCER CELL LINE; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN RNA BINDING; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CARCINOMA, PANCREATIC DUCTAL; DRUG EFFECTS; DRUG RESISTANCE; GENETICS; METABOLISM; PANCREATIC NEOPLASMS; TUMOR CELL LINE;

APOPTOSIS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; ELAV-LIKE PROTEIN 1; HUMANS; PANCREATIC NEOPLASMS; RECEPTORS, TNF-RELATED APOPTOSIS-INDUCING LIGAND; RECOMBINANT PROTEINS; TNF-RELATED APOPTOSIS-INDUCING LIGAND; TRANSFECTION;

EID: 84979944482     PISSN: 15417786     EISSN: 15573125     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-15-0448     Document Type: Article

References (54)

1. Pancreatic Cancer Action Network - Education, Fundraising Advocacy & Patient Services [Internet]. [cited 10/1/2015]. Available from: https://www.pancan.org/.
2. Wong HH, Lemoine NR. Pancreatic cancer: molecular pathogenesis and new therapeutic targets. Nat Rev Gastroenterol Hepatol 2009;6:412-22.
3. 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;29:4548-54.
4. 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;364:1817-25.
5. Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, et al. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 1999;5:157-63.
6. Pineda DM, Rittenhouse DW, Valley CC, Cozzitorto JA, Burkhart RA, Leiby B, et al. HuR's post-transcriptional regulation of Death Receptor 5 in pancreatic cancer cells. Cancer Biol Ther 2012;13:946-55.
7. Satoh K, Kaneko K, Hirota M, Masamune A, Satoh A, Shimosegawa T. Tumor necrosis factor-related apoptosis-inducing ligand and its receptor expression and the pathway of apoptosis in human pancreatic cancer. Pancreas 2001;23:251-8.
8. Lemke J, Noack A, Adam D, Tchikov V, Bertsch U, Roder C, et al. TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5. J Mol Med 2010;88:729-40.
9. Hamacher R, Schmid RM, Saur D, Schneider G. Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol Cancer 2008;7:64.
10. Bin L, Thorburn J, Thomas LR, Clark PE, Humphreys R, Thorburn A. Tumorderived mutations in the TRAIL receptor DR5 inhibit TRAIL signaling through the DR4 receptor by competing for ligand binding. J Biol Chem 2007;282:28189-94.
11. Horak P, Pils D, Kaider A, Pinter A, Elandt K, Sax C, et al. Perturbation of the tumor necrosis factor-related apoptosis-inducing ligand cascade in ovarian cancer: overexpression of FLIPL and deregulation of the functional receptors DR4 and DR5. Clin Cancer Res 2005;11(24 Pt 1):8585-91.
12. Bae SI, Cheriyath V, Jacobs BS, Reu FJ, Borden EC. Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28melanoma cells to interferons (IFNs) or Apo2L/TRAIL. Oncogene 2008;27:490-8.
13. Rubio-Moscardo F, Blesa D, Mestre C, Siebert R, Balasas T, Benito A, et al. Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes. Blood 2005;106:3214-22.
14. Gallmeier E, Bader DC, Kriegl L, Berezowska S, Seeliger H, Goke B, et al. Loss of TRAIL-receptors is a recurrent feature in pancreatic cancer and determines the prognosis of patients with no nodalmetastasis after surgery. PLoS ONE 2013;8:e56760.
15. Buneker C, Mohr A, Zwacka RM. The TRAIL-receptor-1: TRAIL-receptor-3 and -4 ratio is a predictor for TRAIL sensitivity of cancer cells. Oncol Rep 2009;21:1289-95.
16. Strater J, Hinz U, Walczak H, Mechtersheimer G, Koretz K, Herfarth C, et al. Expression of TRAIL and TRAIL receptors in colon carcinoma: TRAIL-R1 is an independent prognostic parameter. Clin Cancer Res 2002;8:3734-40.
17. Lopez de Silanes I, Lal A, Gorospe M. HuR: post-transcriptional paths to malignancy. RNA Biol 2005;2:11-3.
18. Burkhart RA, Pineda DM, Chand SN, Romeo C, Londin ER, Karoly ED, et al. HuR is a post-transcriptional regulator of core metabolic enzymes in pancreatic cancer. RNA Biol 2013;10:1312-23.
19. Costantino CL, Witkiewicz AK, Kuwano Y, Cozzitorto JA, Kennedy EP, Dasgupta A, et al. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR Up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Cancer Res 2009;69:4567-72.
20. Richards NG, Rittenhouse DW, Freydin B, Cozzitorto JA, Grenda D, Rui H, et al. HuR status is a powerful marker for prognosis and response to gemcitabine-based chemotherapy for resected pancreatic ductal adenocarcinoma patients. Ann Surg 2010;252:499-505.
21. Abdelmohsen K, Gorospe M. Posttranscriptional regulation of cancer traits by HuR. Wiley Interdiscip Rev RNA 2010;1:214-29.
22. Kullmann M, Gopfert U, Siewe B, Hengst L. ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 50UTR. Genes Dev 2002;16:3087-99.
23. Leandersson K, Riesbeck K, Andersson T. Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells. Nucleic Acids Res 2006;34:3988-99.
24. Abdelmohsen K, Lal A, Kim HH, Gorospe M. Posttranscriptional orchestration of an anti-apoptotic program by HuR. Cell Cycle 2007;6:1288-92.
25. Mazroui R, Di Marco S, Clair E, von Roretz C, Tenenbaum SA, Keene JD, et al. Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. J Cell Biol 2008;180:113-27.
26. Meisner NC, Hintersteiner M, Mueller K, Bauer R, Seifert JM, Naegeli HU, et al. Identification and mechanistic characterization of low-molecularweight inhibitors for HuR. Nat Chem Biol 2007;3:508-15.
27. Yoo PS, Sullivan CA, Kiang S, Gao W, Uchio EM, Chung GG, et al. Tissue microarray analysis of 560 patients with colorectal adenocarcinoma: high expression of HuR predicts poor survival. Ann Surg Oncol 2009;16:200-7.
28. Talwar S, Jin J, Carroll B, Liu A, Gillespie MB, Palanisamy V. Caspasemediated cleavage of RNA-binding protein HuR regulates c-Myc protein expression after hypoxic stress. J Biol Chem 2011;286:32333-43.
29. Blanco F, Jimbo M, Wulfkuhle J, Gallagher I, Deng J, Enyenihi L, et al. The mRNA-binding protein HuR promotes hypoxia-induced chemoresistance through posttranscriptional regulation of the proto-oncogene PIM1 in pancreatic cancer cells. Oncogene 2015 Sep. 21. [Epub ahead of print].
30. Cozzitorto JA, Jimbo M, Chand S, Blanco F, Lal S, Gilbert M, et al. Studying RNA-binding protein interactions with target mRNAs in eukaryotic cells: native ribonucleoproteinimmunoprecipitation (RIP) assays. MethodsMol Biol 2015;1262:239-46.
31. DeCicco D, Zhu H, Brureau A, Schwaber JS, Vadigepalli R. MicroRNA network changes in the brain stem underlie the development of hypertension. Physiol Genomics 2015;47:388-99.
32. R: The R Project for Statistical Computing [Internet]. [cited 9/11/2015]. Available from: https://www.r-project.org/.
33. Lal S, Burkhart RA, Beeharry N, Bhattacharjee V, Londin ER, Cozzitorto JA, et al. HuR posttranscriptionally regulates WEE1: implications for the DNA damage response in pancreatic cancer cells. Cancer Res 2014;74:1128-40.
34. Williams TK, Costantino CL, Bildzukewicz NA, Richards NG, Rittenhouse DW, Einstein L, et al. pp32 (ANP32A) expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting HuR binding to mRNAs. PLoS ONE 2010;5:e15455.
35. Myer VE, Fan XC, Steitz JA. Identification of HuR as a protein implicated in AUUUA-mediated mRNA decay. EMBO J 1997;16:2130-9.
36. Zhu H, Berkova Z, Mathur R, Sehgal L, Khashab T, Tao R, et al. HuR suppresses Fas expression and correlates with patient outcome in liver cancer. Mol Cancer Res 2015;3:809.
37. Siegmund D, Klose S, Zhou D, Baumann B, Roder C, Kalthoff H, et al. Role of caspases in CD95L- and TRAIL-induced non-apoptotic signalling in pancreatic tumour cells. Cell Signal 2007;19:1172-84.
38. Winkler C, Doller A, Imre G, Badawi A, Schmid T, Schulz S, et al. Attenuation of the ELAV1-like protein HuR sensitizes adenocarcinoma cells to the intrinsic apoptotic pathway by increasing the translation of caspase-2L. Cell Death Dis 2014;5:e1321.
39. Tatsuta K, Yoshimoto T, Gunji H. Total synthesis of MS-444, a myosin light chain kinase inhibitor. J Antibiot 1997;50:289-90.
40. Tatsuta K, Nakanishi S, Takahashi I. Preparation of MS-444 derivatives as immunosuppressive and anti-itching agents. (Kyowa Hakko Kogyo Co., Ltd., Japan). Application: WO 9832750, AI 19980730, CAN 129:148903, AN 1998:527326, 1998.
41. Slee EA, Adrain C, Martin SJ. Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. J Biol Chem 2001;276:7320-6.
42. Gurzov EN, Ortis F, Bakiri L, Wagner EF, Eizirik DL. JunB inhibits ER stress and apoptosis in pancreatic beta cells. PLoS ONE 2008;3:e3030.
43. Zhao X, Liu Y, Ma Q, Wang X, Jin H, Mehrpour M, et al. Caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells. Biochem Biophys Res Commun 2009;378:21-6.
44. Dimberg LY, Anderson CK, Camidge R, Behbakht K, Thorburn A, Ford HL. On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics. Oncogene 2013;32:1341-50.
45. Mohammed A, Janakiram NB, Pant S, Rao CV. Molecular targeted intervention for pancreatic cancer. Cancers 2015;7:1499-542.
46. Gallouzi IE, Brennan CM, Steitz JA. Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. RNA 2001;7:1348-61.
47. Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL, Gorospe M. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev 2009;23:1743-8.
48. Abdelmohsen K, Srikantan S, Kuwano Y, Gorospe M. miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proc Natl Acad Sci U S A 2008;105:20297-302.
49. Kang MJ, Ryu BK, Lee MG, Han J, Lee JH, Ha TK, et al. NF-kappaB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis. Gastroenterology 2008;135:2030-42.
50. Harper N, Farrow SN, Kaptein A, Cohen GM, MacFarlane M. Modulation of tumor necrosis factor apoptosis-inducing ligand-induced NF-kappa B activation by inhibition of apical caspases. J Biol Chem 2001;276:34743-52.
51. Doller A, Huwiler A, Muller R, Radeke HH, Pfeilschifter J, Eberhardt W. Protein kinase C alpha-dependent phosphorylation of the mRNA-stabilizing factor HuR: implications for posttranscriptional regulation of cyclooxygenase-2. Mol Biol Cell 2007;18:2137-48.
52. Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 2006;25:4798-811.
53. Wu X, Lan L, Wilson DM, Marquez RT, Tsao WC, Gao P, et al. Identification and validation of novel small molecule disruptors of HuR-mRNA interaction. ACS Chem Biol 2015;10:1476-84.
54. Huang Y-H, Peng W, Furuuchi N, Gerhart J, Rhodes K, Mukherjee N, et al. Delivery of therapeutics tarageting the mRNAS-binding protein HuR using 3DNA nancarriers suppresses ovarian tumor growth. Cancer Res 2016;76:1549-59.