PP2A inhibitors suppress migration and growth of PANC-1 pancreatic cancer cells through inhibition on the Wnt/β-catenin pathway by phosphorylation and degradation of β-catenin

Oncology Reports

Volumn 32, Issue 2, 2014, Pages 513-522

  Wu, Meng Yao ^a   Xie, Xin ^a,d   Xu, Ze Kuan ^b   Xie, Li ^b   Chen, Zheng ^b   Shou, Liu Mei ^a   Gong, Fei Ran ^a   Xie, Yu Feng ^a   Li, Wei ^a,b   Tao, Min ^a,c  

^a THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIVERSITY   (China)

^b THE FIRST AFFILIATED HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

^c Institute of Clinical Immunology of Jiangsu Province   (China)

^d XUZHOU MEDICAL UNIVERSITY   (China)

Author keywords

Pancreatic cancer; Phosphorylation; PP2A; Wnt catenin signal pathway

Indexed keywords

ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; ANTINEOPLASTIC AGENT; BETA CATENIN; CANTHARIDIN; NORCANTHARIDIN; OKADAIC ACID; PROTEIN PHOSPHATASE 2A INHIBITOR; UNCLASSIFIED DRUG; WNT PROTEIN; ANTHRA(1,9-CD)PYRAZOL-6(2H)-ONE; ANTHRACENE DERIVATIVE; ENZYME INHIBITOR; FH535; PHOSPHOPROTEIN PHOSPHATASE 2; SULFONAMIDE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CACNALG GENE; CANCER INHIBITION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; DKK3 GENE; ENZYME REPRESSION; GENE EXPRESSION REGULATION; HUMAN; HUMAN CELL; KRT8 GENE; MICROARRAY ANALYSIS; NRP1 GENE; ONCOGENE; PANCREAS CANCER; PANCREATIC CANCER CELL LINE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; VEGFB GENE; WESTERN BLOTTING; WISP2 GENE; ANTAGONISTS AND INHIBITORS; CELL MOTION; DRUG EFFECTS; GENETICS; METABOLISM; PANCREATIC NEOPLASMS; PATHOLOGY; PHOSPHORYLATION; WNT SIGNALING PATHWAY;

ANTHRACENES; BETA CATENIN; CANTHARIDIN; CELL MOVEMENT; CELL PROLIFERATION; ENZYME INHIBITORS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; PANCREATIC NEOPLASMS; PHOSPHORYLATION; PROTEIN PHOSPHATASE 2; SULFONAMIDES; WNT SIGNALING PATHWAY;

EID: 84903150694     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or.2014.3266     Document Type: Article

References (55)

1. Wolfgang CL, Herman JM, Laheru DA, et al: Recent progress in pancreatic cancer. CA Cancer J Clin 63: 318-348, 2013.
2. Paulson AS, Tran Cao HS, Tempero MA and Lowy AM: Therapeutic advances in pancreatic cancer. Gastroenterology 144: 1316-1326, 2013.
3. Li W, Xie L, Chen Z, et al: Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci 101: 1226-1233, 2010.
4. Li W, Chen Z, Zong Y, et al: PP2A inhibitors induce apoptosis in pancreatic cancer cell line PANC-1 through persistent phosphorylation of IKKα and sustained activation of the NF-KB pathway. Cancer Lett 304: 117-127, 2011.
5. Li W, Chen Z, Gong FR, et al: Growth of the pancreatic cancer cell line PANC-1 is inhibited by protein phosphatase 2A inhibitors through overactivation of the c-Jun N-terminal kinase pathway. Eur J Cancer 47: 2654-2664, 2011.
6. Shou LM, Zhang QY, Li W, et al: Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin. Oncol Rep 30: 1059-1066, 2013.
7. Clevers H and Nusse R: Wnt/beta-catenin signaling and disease. Cell 149: 1192-1205, 2012.
8. MacDonald BT, Tamai K and He X: Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17: 9-26, 2009.
9. Nelson WJ and Nusse R: Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303: 1483-1487, 2004. (Pubitemid 38314410)
10. Fearon ER: PARsing the phrase "all in for Axin"- Wnt pathway targets in cancer. Cancer Cell 16: 366-368, 2009.
11. White BD, Chien AJ and Dawson DW: Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers. Gastroenterology 142: 219-232, 2012.
12. Bos CL, Kodach LL, van den Brink GR, et al: Effect of aspirin on the Wnt/β-catenin pathway is mediated via protein phosphatase 2A. Oncogene 25: 6447-6456, 2006. (Pubitemid 44607077)
13. Carmichael J, DeGraff WG, Gazdar AF, Minna JD and Mitchell JB: Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 47: 936-942, 1987. (Pubitemid 17027905)
14. Huang C, Jacobson K and Schaller MD: MAP kinases and cell migration. J Cell Sci 117: 4619-4628, 2004. (Pubitemid 39433429)
15. Handeli S and Simon JA: A small-molecule inhibitor of Tcf/beta-catenin signaling down-regulates PPARgamma and PPARdelta activities. Mol Cancer Ther 7: 521-529, 2008. (Pubitemid 351482135)
16. Turashvili G, Bouchal J, Burkadze G and Kolar Z: Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology 73: 213-223, 2006. (Pubitemid 46332829)
17. Yamaguchi TP: Heads or tails: Wnts and anterior-posterior patterning. Curr Biol 11: R713-R724, 2001.
18. Tetsu O and McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398: 422-426, 1999. (Pubitemid 29180374)
19. Clevers H: Wnt/beta-catenin signaling in development and disease. Cell 127: 469-480, 2006.
20. Polakis P: Wnt signaling and cancer. Genes Dev 14: 1837-1851, 2000.
21. Takahashi-Yanaga F and Sasaguri T: GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy. Cell Signal 20: 581-589, 2008. (Pubitemid 351241128)
22. Papadopoulou S and Edlund H: Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic function. Diabetes 54: 2844-2851, 2005. (Pubitemid 41401078)
23. Zeng G, Germinaro M, Micsenyi A, et al: Aberrant Wnt/betacatenin signaling in pancreatic adenocarcinoma. Neoplasia 8: 279-289, 2006.
24. Chetty R, Serra S, Salahshor S, et al: Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis. Hum Pathol 37: 212-217, 2006. (Pubitemid 43099842)
25. Pasca di Magliano M, Biankin AV, Heiser PW, et al: Common activation of canonical Wnt signaling in pancreatic adenocarcinoma. PloS One 2: e1155, 2007.
26. Wang L, Heidt DG, Lee CJ, et al: Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and beta-catenin stabilization. Cancer Cell 15: 207-219, 2009.
27. Lowy AM, Fenoglio-Preiser C, Kim OJ, et al: Dysregulation of beta-catenin expression correlates with tumor differentiation in pancreatic duct adenocarcinoma. Ann Surg Oncol 10: 284-290, 2003. (Pubitemid 40486962)
28. Joo YE, Rew JS, Park CS and Kim SJ: Expression of E-cadherin, alpha- and beta-catenins in patients with pancreatic adenocarcinoma. Pancreatology 2: 129-137, 2002.
29. Karayiannakis AJ, Syrigos KN, Polychronidis A and Simopoulos C: Expression patterns of alpha-, beta- and gamma-catenin in pancreatic cancer: correlation with E-cadherin expression, pathological features and prognosis. Anticancer Res 21: 4127-4134, 2001. (Pubitemid 34229299)
30. Li YJ, Wei ZM, Meng YX and Ji XR: Beta-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis. World J Gastroenterol 11: 2117-2123, 2005.
31. Qiao Q, Ramadani M, Gansauge S, Gansauge F, Leder G and Beger HG: Reduced membranous and ectopic cytoplasmic expression of beta -catenin correlate with cyclin D1 overexpression and poor prognosis in pancreatic cancer. Int J Cancer 95: 194-197, 2001. (Pubitemid 32477236)
32. Heiser PW, Cano DA, Landsman L, et al: Stabilization of beta-catenin induces pancreas tumor formation. Gastroenterology 135: 1288-1300, 2008.
33. Seeling JM, Miller JR, Gil R, Moon RT, White R and Virshup DM: Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A. Science 283: 2089-2091, 1999.
34. Li X, Yost HJ, Virshup DM and Seeling JM: Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J 20: 4122-4131, 2001. (Pubitemid 32751828)
35. Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med 9: 669-676, 2003. (Pubitemid 36749215)
36. Wey JS, Fan F, Gray MJ, et al: Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines. Cancer 104: 427-438, 2005. (Pubitemid 40993273)
37. Bielenberg DR, Pettaway CA, Takashima S and Klagsbrun M: Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res 312: 584-593, 2006. (Pubitemid 43290335)
38. Frankel P, Pellet-Many C, Lehtolainen P, et al: Chondroitin sulphate-modified neuropilin 1 is expressed in human tumour cells and modulates 3D invasion in the U87MG human glioblastoma cell line through a p130Cas-mediated pathway. EMBO Rep 9: 983-989, 2008.
39. Miao HQ, Lee P, Lin H, Soker S and Klagsbrun M: Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression. FASEB J 14: 2532-2539, 2000.
40. Wey JS, Gray MJ, Fan F, et al: Overexpression of neuropilin-1 promotes constitutive MAPK signalling and chemoresistance in pancreatic cancer cells. Br J Cancer 93: 233-241, 2005. (Pubitemid 41133210)
41. Latil A, Bieche I, Pesche S, et al: VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms. Int J Cancer 89: 167-171, 2000. (Pubitemid 30185926)
42. Hansel DE, Wilentz RE, Yeo CJ, Schulick RD, Montgomery E and Maitra A: Expression of neuropilin-1 in high-grade dysplasia, invasive cancer, and metastases of the human gastrointestinal tract. Am J Surg Pathol 28: 347-356, 2004. (Pubitemid 38269568)
43. Ochiumi T, Kitadai Y, Tanaka S, Akagi M, Yoshihara M and Chayama K: Neuropilin-1 is involved in regulation of apoptosis and migration of human colon cancer. Int J Oncol 29: 105-116, 2006.
44. Zenzmaier C, Hermann M, Hengster P and Berger P: Dickkopf-3 maintains the PANC-1 human pancreatic tumor cells in a dedifferentiated state. Int J Oncol 40: 40-46, 2012.
45. Fortier AM, Asselin E and Cadrin M: Keratin 8 and 18 loss in epithelial cancer cells increases collective cell migration and cisplatin sensitivity through claudin1 up-regulation. J Biol Chem 288: 11555-11571, 2013.
46. Toyota M, Ho C, Ohe-Toyota M, Baylin SB and Issa JP: Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5′ CpG island in human tumors. Cancer Res 59: 4535-4541, 1999. (Pubitemid 29428953)
47. Lory P, Bidaud I and Chemin J: T-type calcium channels in differentiation and proliferation. Cell Calcium 40: 135-146, 2006. (Pubitemid 43964483)
48. Panner A and Wurster RD: T-type calcium channels and tumor proliferation. Cell calcium 40: 253-259, 2006. (Pubitemid 43942305)
49. 2+ channels suppresses human breast cancer cell proliferation. Cancer Lett 267: 116-124, 2008.
50. 2+ channels by endostatin attenuates human glioblastoma cell proliferation and migration. Br J Pharmacol 166: 1247-1260, 2012.
51. Brigstock DR: The CCN family: a new stimulus package. J Endocrinol 178: 169-175, 2003.
52. Davies SR, Davies ML, Sanders A, Parr C, Torkington J and Jiang WG: Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications. Int J Oncol 36: 1129-1136, 2010.
53. Aikawa T, Gunn J, Spong SM, Klaus SJ and Korc M: Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther 5: 1108-1116, 2006. (Pubitemid 43881302)
54. Millward TA, Zolnierowicz S and Hemmings BA: Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci 24: 186-191, 1999. (Pubitemid 29348452)
55. Janssens V, Goris J and Van Hoof C: PP2A: the expected tumor suppressor. Curr Opin Genet Dev 15: 34-41, 2005. (Pubitemid 40127629)