Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine

Cancer Biology and Therapy

Volumn 14, Issue 6, 2013, Pages 492-501

  Xu, Dapeng ^a   Cobb, Michael G ^b   Gavilano, Lily ^b   Witherspoon, Sam M ^b   Williams, Daniel ^b   White, Catherine D ^b   Taverna, Pietro ^c   Bednarski, Brian K ^d   Kim, Hong Jin ^e,f   Baldwin, Albert S ^e   Baines, Antonio T ^b,e,f  

^a XIAMEN UNIVERSITY   (China)

^b NORTH CAROLINA CENTRAL UNIVERSITY   (United States)

^c NORTH CAROLINA A AND T STATE UNIVERSITY   (United States)

^d ASTEX PHARMACEUTICALS   (United Kingdom)

^e UNIVERSITY OF NORTH CAROLINA   (United States)

^f UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Chemoresistance; Chemosensitivity; Gemcitabine; Pancreatic cancer; Pim kinase; Pim 3 kinase; Transformed growth

Indexed keywords

CASPASE 3; GEMCITABINE; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN BAD; PROTEIN KINASE PIM 1; PROTEIN KINASE PIM 3; PROTEIN SERINE THREONINE KINASE; PUROMYCIN; SGI 1776; UNCLASSIFIED DRUG; ANTINEOPLASTIC ANTIMETABOLITE; BAD PROTEIN, HUMAN; DEOXYCYTIDINE; IMIDAZOLE DERIVATIVE; ONCOPROTEIN; PIM3 PROTEIN, HUMAN; PYRIDAZINE DERIVATIVE; SMALL INTERFERING RNA;

ANCHORAGE INDEPENDENT GROWTH; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER GROWTH; CANCER INHIBITION; CANCER RESISTANCE; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CELL VIABILITY; CHEMOSENSITIZATION; CLINICAL ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG SENSITIVITY; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; ONCOGENE; PANCREAS ADENOCARCINOMA; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; TUMOR INVASION; UPREGULATION; WESTERN BLOTTING; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; CARCINOMA, PANCREATIC DUCTAL; DRUG EFFECTS; DRUG POTENTIATION; DRUG RESISTANCE; ENZYMOLOGY; GENE EXPRESSION; GENE SILENCING; GENETICS; METABOLISM; PANCREATIC NEOPLASMS; PATHOLOGY; PHOSPHORYLATION; PROTEIN PROCESSING; TUMOR CELL LINE;

ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; BCL-ASSOCIATED DEATH PROTEIN; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CELL PROLIFERATION; DEOXYCYTIDINE; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; GENE EXPRESSION; GENE KNOCKDOWN TECHNIQUES; HUMANS; IMIDAZOLES; NEOPLASM INVASIVENESS; PANCREATIC NEOPLASMS; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PYRIDAZINES; RNA, SMALL INTERFERING;

EID: 84879176690     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.24343     Document Type: Article

References (36)

1. Cancer Facts & Figures 2012. Atlanta: American Cancer Society 2012.
2. Liu QH, Zhang J, Zhao CY, Yu DH, Bu HJ, Chen Y, et al. Surviving cells after treatment with gemcitabine or 5-fluorouracil for the study of de novo resistance of pancreatic cancer. Cancer Lett 2012; 314:119-25; PMID:21983131; http://dx.doi.org/10.1016/j.canlet. 2011.09.018.
3. Mukaida N, Wang YY, Li YY. Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer Sci 2011; 102:1437-42; PMID:21518143; http://dx.doi.org/ 10.1111/j.1349-7006.2011.01966.x.
4. Feldman JD, Vician L, Crispino M, Tocco G, Marcheselli VL, Bazan NG, et al. KID-1, a protein kinase induced by depolarization in brain. J Biol Chem 1998; 273:16535-43; PMID:9632723; http://dx.doi.org/10.1074/jbc.273.26.16535.
5. Nawijn MC, Alendar A, Berns A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer 2011; 11:23-34; PMID:21150935; http://dx.doi.org/10.1038/nrc2986.
6. Fujii C, Nakamoto Y, Lu P, Tsuneyama K, Popivanova BK, Kaneko S, et al. Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines. Int J Cancer 2005; 114:209-18; PMID:15540201; http://dx.doi.org/10.1002/ijc.20719.
7. Popivanova BK, Li YY, Zheng H, Omura K, Fujii C, Tsuneyama K, et al. Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Badmediated apoptosis. Cancer Sci 2007; 98:321-8; PMID:17270021; http://dx.doi.org/10.1111/j.1349-7006. 2007.00390.x.
8. Zheng HC, Tsuneyama K, Takahashi H, Miwa S, Sugiyama T, Popivanova BK, et al. Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression. J Cancer Res Clin Oncol 2008; 134:481-8; PMID:17876606; http://dx.doi.org/10.1007/s00432-007-0310-1.
9. Li YY, Popivanova BK, Nagai Y, Ishikura H, Fujii C, Mukaida N. Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block badmediated apoptosis in human pancreatic cancer cell lines. Cancer Res 2006; 66:6741-7; PMID:16818649; http://dx.doi.org/10.1158/0008-5472.CAN-05-4272.
10. Deneen B, Welford SM, Ho T, Hernandez F, Kurland I, Denny CT. PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Mol Cell Biol 2003; 23:3897-908; PMID:12748291; http://dx.doi.org/10.1128/MCB.23.11.3897-3908.2003.
11. Li YY, Wu Y, Tsuneyama K, Baba T, Mukaida N. Essential contribution of Ets-1 to constitutive Pim-3 expression in human pancreatic cancer cells. Cancer Sci 2009; 100:396-404; PMID:19154409; http://dx.doi.org/10.1111/j.1349-7006. 2008.01059.x.
12. Chang M, Kanwar N, Feng E, Siu A, Liu X, Ma D, et al. PIM kinase inhibitors downregulate STAT3(Tyr705) phosphorylation. Mol Cancer Ther 2010; 9:2478-87; PMID:20667852; http://dx.doi.org/10.1158/1535-7163.MCT-10-0321.
13. Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999; 10:105-15; PMID:10023775; http://dx.doi.org/10.1016/S1074-7613(00)80011-4.
14. Duan Z, Foster R, Bell DA, Mahoney J, Wolak K, Vaidya A, et al. Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res 2006; 12:5055-63; PMID:16951221; http://dx.doi.org/10.1158/1078-0432.CCR-06-0861.
15. Lai SYJF, Johnson FM. Defining the role of the JAKSTAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Drug Resist Updat 2010; 13:67-78; PMID:20471303; http://dx.doi.org/10.1016/j.drup.2010.04.001.
16. Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res 2006; 12:11-9; PMID:16397018; http://dx.doi.org/10.1158/1078-0432.CCR-04-1752.
17. Chen J, Kobayashi M, Darmanin S, Qiao Y, Gully C, Zhao R, et al. Pim-1 plays a pivotal role in hypoxiainduced chemoresistance. Oncogene 2009; 28:2581-92; PMID:19483729; http://dx.doi.org/10.1038/onc.2009.124.
18. Macdonald A, Campbell DG, Toth R, McLauchlan H, Hastie CJ, Arthur JS. Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. BMC Cell Biol 2006; 7:1; PMID:16403219; http://dx.doi.org/10.1186/1471-2121-7-1.
19. Campbell PM, Groehler AL, Lee KM, Ouellette MM, Khazak V, Der CJ. K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling. Cancer Res 2007; 67:2098-106; PMID:17332339; http://dx.doi.org/10.1158/0008-5472.CAN-06-3752.
20. Abiatari I, DeOliveira T, Kerkadze V, Schwager C, Esposito I, Giese NA, et al. Consensus transcriptome signature of perineural invasion in pancreatic carcinoma. Mol Cancer Ther 2009; 8:1494-504; PMID:19509238; http://dx.doi.org/ 10.1158/1535-7163.MCT-08-0755.
21. Mumenthaler SM, Ng PY, Hodge A, Bearss D, Berk G, Kanekal S, et al. Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther 2009; 8:2882-93; PMID:19825806; http://dx.doi.org/10.1158/1535-7163.MCT-09-0293.
22. Isaac M, Siu A, Jongstra J. The oncogenic PIM kinase family regulates drug resistance through multiple mechanisms. Drug Resist Updat 2011; 14:203-11; PMID:21601509; http://dx.doi.org/10.1016/j.drup.2011.04.002.
23. Brault L, Gasser C, Bracher F, Huber K, Knapp S, Schwaller J. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Haematologica 2010; 95:1004-15; PMID:20145274; http://dx.doi.org/10.3324/haematol. 2009.017079.
24. Magnuson NS, Wang Z, Ding G, Reeves R. Why target PIM1 for cancer diagnosis and treatment? Future Oncol 2010; 6:1461-78; PMID:20919829; http://dx.doi.org/10.2217/fon.10.106.
25. Yang XY, Ren CP, Wang L, Li H, Jiang CJ, Zhang HB, et al. Identification of differentially expressed genes in metastatic and non-metastatic nasopharyngeal carcinoma cells by suppression subtractive hybridization. Cell Oncol 2005; 27:215-23; PMID:16308470.
26. Chen J, Kobayashi M, Darmanin S, Qiao Y, Gully C, Zhao R, et al. Hypoxia-mediated up-regulation of Pim-1 contributes to solid tumor formation. Am J Pathol 2009; 175:400-11; PMID:19528349; http://dx.doi.org/10.2353/ajpath. 2009.080972.
27. Xu D, Allsop SA, Witherspoon SM, Snider JL, Yeh JJ, Fiordalisi JJ, et al. The oncogenic kinase Pim-1 is modulated by K-Ras signaling and mediates transformed growth and radioresistance in human pancreatic ductal adenocarcinoma cells. Carcinogenesis 2011; 32:488-95; PMID:21262926; http://dx.doi.org/10. 1093/carcin/bgr007.
28. Demols A, Peeters M, Polus M, Marechal R, Gay F, Monsaert E, et al. Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer 2006; 94:481-5; PMID:16434988; http://dx.doi.org/10.1038/sj.bjc.6602966.
29. Haddach M MJ, Schwaebe MK, Pierre F, O'Brien SE, Borsan C et al. Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor. ACS Medicinal Chemistry Letters 2012; 3:135-9; http://dx.doi.org/10.1021/ml200259q.
30. Swords R, Kelly K, Carew J, Nawrocki S, Mahalingam D, Sarantopoulos J, et al. The Pim kinases: new targets for drug development. Curr Drug Targets 2011; 12:2059-66; PMID:21777193; http://dx.doi.org/10.2174/138945011798829447.
31. Chen LS, Redkar S, Bearss D, Wierda WG, Gandhi V. Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood 2009; 114:4150-7; PMID:19734450; http://dx.doi.org/10.1182/blood-2009-03-212852.
32. Song JH, Kraft AS. Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737. Cancer Res 2012; 72:294-303; PMID:22080570; http://dx.doi.org/10.1158/0008-5472.CAN-11-3240.
33. Giroux V, Malicet C, Barthet M, Gironella M, Archange C, Dagorn JC, et al. p8 is a new target of gemcitabine in pancreatic cancer cells. Clin Cancer Res 2006; 12:235-41; PMID:16397047; http://dx.doi.org/10.1158/1078-0432.CCR-05- 1700.
34. Wang YY, Taniguchi T, Baba T, Li YY, Ishibashi H, Mukaida N. Identification of a phenanthrene derivative as a potent anticancer drug with Pim kinase inhibitory activity. Cancer Sci 2012; 103:107-15; PMID:21981263; http://dx.doi.org/10.1111/j.1349-7006.2011.02117.x.
35. Reiser-Erkan C, Erkan M, Pan Z, Bekasi S, Giese NA, Streit S, et al. Hypoxia-inducible proto-oncogene Pim-1 is a prognostic marker in pancreatic ductal adenocarcinoma. Cancer Biol Ther 2008; 7:1352-9; PMID:18708761; http://dx.doi.org/10.4161/cbt.7.9.6418.
36. Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 2006; 124:1283-98; PMID:16564017; http://dx.doi.org/ 10.1016/j.cell.2006.01.040.