PP2A inhibition overcomes acquired resistance to HER2 targeted therapy

Molecular Cancer

Volumn 13, Issue 1, 2014, Pages

  McDermott, Martina S J ^a   Browne, Brigid C ^b   Conlon, Neil T ^a   O'Brien, Neil A ^c   Slamon, Dennis J ^c   Henry, Michael ^a   Meleady, Paula ^a   Clynes, Martin ^a   Dowling, Paul ^a,d   Crown, John ^a,e   O'Donovan, Norma ^a  

^a DUBLIN CITY UNIVERSITY   (Ireland)

^b GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d NATIONAL UNIVERSITY OF IRELAND   (Ireland)

^e ST VINCENT S UNIVERSITY HOSPITAL   (Ireland)

Author keywords

eEF2; HER2; lapatinib; PP2A; Resistance

Indexed keywords

ELONGATION FACTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FINGOLIMOD; GEFITINIB; LAPATINIB; OKADAIC ACID; PHOSPHOPROTEIN PHOSPHATASE 2A; TRASTUZUMAB; ELONGATION FACTOR 2 KINASE; ERBB2 PROTEIN, HUMAN; MONOCLONAL ANTIBODY; PHOSPHOPROTEIN PHOSPHATASE 2; QUINAZOLINE DERIVATIVE;

ARTICLE; BREAST CANCER; BREAST CANCER CELL LINE; CANCER INHIBITION; CANCER RESISTANCE; CELL CYCLE ASSAY; CONTROLLED STUDY; CROSS RESISTANCE; DRUG MECHANISM; DRUG SENSITIVITY; ENZYME INHIBITION; IC 50; LOW DRUG DOSE; MOLECULARLY TARGETED THERAPY; PHOSPHOPROTEOMIC PROFILING; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; PROTEOMICS; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; DRUG EFFECTS; DRUG RESISTANCE; FEMALE; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM; PATHOLOGY; PHOSPHORYLATION; TUMOR CELL LINE;

ANTIBODIES, MONOCLONAL, HUMANIZED; BREAST NEOPLASMS; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; ELONGATION FACTOR 2 KINASE; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; PHOSPHORYLATION; PROTEIN PHOSPHATASE 2; PROTEOMICS; QUINAZOLINES; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION;

EID: 84903691855     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-13-157     Document Type: Article

References (50)

1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235(4785):177-182. 10.1126/science.3798106, 3798106.
2. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005, 5(5):341-354. 10.1038/nrc1609, 15864276.
3. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 1992, 89(10):4285-4289. 10.1073/pnas.89.10.4285, 49066, 1350088.
4. Xia W, Mullin RJ, Keith BR, Liu LH, Ma H, Rusnak DW, Owens G, Alligood KJ, Spector NL. Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene 2002, 21(41):6255-6263. 10.1038/sj.onc.1205794, 12214266.
5. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001, 344(11):783-792. 10.1056/NEJM200103153441101, 11248153.
6. Gullo G, Zuradelli M, Sclafani F, Santoro A, Crown J. Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer. Ann Oncol 2012, 23(8):2204-2205. 10.1093/annonc/mds221, 22767587.
7. Razis E, Bobos M, Kotoula V, Eleftheraki AG, Kalofonos HP, Pavlakis K, Papakostas P, Aravantinos G, Rigakos G, Efstratiou I, Petraki K, Bafaloukos D, Kostopoulos I, Pectasides D, Kalogeras KT, Skarlos D, Fountzilas G. Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer. Breast Cancer Res Treat 2011, 128(2):447-456. 10.1007/s10549-011-1572-5, 21594665.
8. O'Brien NA, Browne BC, Chow L, Wang Y, Ginther C, Arboleda J, Duffy MJ, Crown J, O'Donovan N, Slamon DJ. Activated Phosphoinositide 3-Kinase/AKT Signaling Confers Resistance to Trastuzumab but not Lapatinib. Mol Cancer Ther 2010, 9(6):1489-1502. 10.1158/1535-7163.MCT-09-1171, 20501798.
9. Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon Y, Cajal S, Arribas J, Baselga J. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst 2007, 99(8):628-638. 10.1093/jnci/djk134, 17440164.
10. Motoyama AB, Hynes NE, Lane HA. The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides. Cancer Res 2002, 62(11):3151-3158.
11. Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 2005, 65(23):11118-11128. 10.1158/0008-5472.CAN-04-3841, 16322262.
12. Browne BC, Crown J, Venkatesan N, Duffy MJ, Clynes M, Slamon D, O'Donovan N. Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells. Ann Oncol 2011, 22(1):68-73. 10.1093/annonc/mdq349, 20647220.
13. Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, Arteaga CL. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res 2007, 13(16):4909-4919. 10.1158/1078-0432.CCR-07-0701, 17699871.
14. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006, 355(26):2733-2743. 10.1056/NEJMoa064320, 17192538.
15. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, Untch M, Rusnak DW, Spehar G, Mullin RJ, Keith BR, Gilmer TM, Berger M, Podratz KC, Slamon DJ. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006, 66(3):1630-1639. 10.1158/0008-5472.CAN-05-1182, 16452222.
16. O'Donovan N, Byrne AT, O'Connor AE, McGee S, Gallagher WM, Crown J. Synergistic interaction between trastuzumab and EGFR/HER-2 tyrosine kinase inhibitors in HER-2 positive breast cancer cells. Invest New Drugs 2011, 29(5):752-759. 10.1007/s10637-010-9415-5, 20229355.
17. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gomez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horvath Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, . NeoALTTO Study Team Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012, 379(9816):633-640. 10.1016/S0140-6736(11)61847-3, 22257673, NeoALTTO Study Team.
18. Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R, Halsey W, Sathe GM, Martin AM, Gilmer TM. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res 2009, 69(17):6871-6878. 10.1158/0008-5472.CAN-08-4490, 19671800.
19. Martin AP, Miller A, Emad L, Rahmani M, Walker T, Mitchell C, Hagan MP, Park MA, Yacoub A, Fisher PB, Grant S, Dent P. Lapatinib resistance in HCT116 cells is mediated by elevated MCL-1 expression and decreased BAK activation and not by ERBB receptor kinase mutation. Mol Pharmacol 2008, 74(3):807-822. 10.1124/mol.108.047365, 2574656, 18544666.
20. Aird KM, Ghanayem RB, Peplinski S, Lyerly HK, Devi GR. X-linked inhibitor of apoptosis protein inhibits apoptosis in inflammatory breast cancer cells with acquired resistance to an ErbB1/2 tyrosine kinase inhibitor. Mol Cancer Ther 2010, 9(5):1432-1442. 10.1158/1535-7163.MCT-10-0160, 2957814, 20406946.
21. Rexer BN, Ham AJ, Rinehart C, Hill S, Granja-Ingram Nde M, Gonzalez-Angulo AM, Mills GB, Dave B, Chang JC, Liebler DC, Arteaga CL. Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition. Oncogene 2011, 30(40):4163-4174. 10.1038/onc.2011.130, 3204390, 21499296.
22. Xia W, Bacus S, Husain I, Liu L, Zhao S, Liu Z, Moseley MA, Thompson JW, Chen FL, Koch KM, Spector NL. Resistance to ErbB2 tyrosine kinase inhibitors in breast cancer is mediated by calcium-dependent activation of RelA. Mol Cancer Ther 2010, 9(2):292-299. 10.1158/1535-7163.MCT-09-1041, 20124457.
23. Xia W, Bacus S, Hegde P, Husain I, Strum J, Liu L, Paulazzo G, Lyass L, Trusk P, Hill J, Harris J, Spector NL. A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc Natl Acad Sci U S A 2006, 103(20):7795-7800. 10.1073/pnas.0602468103, 1472524, 16682622.
24. Jegg AM, Ward TM, Iorns E, Hoe N, Zhou J, Liu X, Singh S, Landgraf R, Pegram MD. PI3K independent activation of mTORC1 as a target in lapatinib-resistant ERBB2+ breast cancer cells. Breast Cancer Res Treat 2012, 136(3):683-692. 10.1007/s10549-012-2252-9, 23089982.
25. Burris HA, Hurwitz HI, Dees EC, Dowlati A, Blackwell KL, O'Neil B, Marcom PK, Ellis MJ, Overmoyer B, Jones SF, Harris JL, Smith DA, Koch KM, Stead A, Mangum S, Spector NL. Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol 2005, 23(23):5305-5313. 10.1200/JCO.2005.16.584, 15955900.
26. Huang C, Park CC, Hilsenbeck SG, Ward R, Rimawi MF, Wang YC, Shou J, Bissell MJ, Osborne CK, Schiff R. Beta1 Integrin mediates an alternative survival pathway in breast cancer cells resistant to lapatinib. Breast Cancer Res 2011, 13(4):R84. 10.1186/bcr2936, 3236347, 21884573.
27. Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, Beijersbergen RL, Valero V, Seoane J, Bernards R, Baselga J. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 2008, 68(22):9221-9230. 10.1158/0008-5472.CAN-08-1740, 2587064, 19010894.
28. Eustace AJ, Dowling P, Henry M, Doolan P, Meleady P, Clynes M, Crown J, O'Donovan N. 2D-DIGE analysis of phospho-enriched fractions from dasatinib-treated melanoma cell lines. J Proteomics 2011, 74(4):490-501. 10.1016/j.jprot.2010.12.011, 21237296.
29. Carlberg U, Nilsson A, Nygard O. Functional properties of phosphorylated elongation factor 2. Eur J Biochem 1990, 191(3):639-645. 10.1111/j.1432-1033.1990.tb19169.x, 2390990.
30. Ryazanov AG, Davydova EK. Mechanism of elongation factor 2 (EF-2) inactivation upon phosphorylation. Phosphorylated EF-2 is unable to catalyze translocation. FEBS Lett 1989, 251(1-2):187-190.
31. Browne GJ, Proud CG. Regulation of peptide-chain elongation in mammalian cells. Eur J Biochem 2002, 269(22):5360-5368. 10.1046/j.1432-1033.2002.03290.x, 12423334.
32. Knebel A, Morrice N, Cohen P. A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. EMBO J 2001, 20(16):4360-4369. 10.1093/emboj/20.16.4360, 125581, 11500363.
33. Arora S, Yang JM, Kinzy TG, Utsumi R, Okamoto T, Kitayama T, Ortiz PA, Hait WN. Identification and characterization of an inhibitor of eukaryotic elongation factor 2 kinase against human cancer cell lines. Cancer Res 2003, 63(20):6894-6899.
34. Hizli AA, Chi Y, Swanger J, Carter JH, Liao Y, Welcker M, Ryazanov AG, Clurman BE. Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase. Mol Cell Biol 2013, 33(3):596-604. 10.1128/MCB.01270-12, 3554216, 23184662.
35. Westermarck J, Hahn WC. Multiple pathways regulated by the tumor suppressor PP2A in transformation. Trends Mol Med 2008, 14(4):152-160. 10.1016/j.molmed.2008.02.001, 18329957.
36. Gergs U, Boknik P, Buchwalow I, Fabritz L, Matus M, Justus I, Hanske G, Schmitz W, Neumann J. Overexpression of the catalytic subunit of protein phosphatase 2A impairs cardiac function. J Biol Chem 2004, 279(39):40827-40834. 10.1074/jbc.M405770200, 15247211.
37. Everett AD, Stoops TD, Nairn AC, Brautigan D. Angiotensin II regulates phosphorylation of translation elongation factor-2 in cardiac myocytes. Am J Physiol Heart Circ Physiol 2001, 281(1):H161-H167.
38. Bialojan C, Takai A. Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics. Biochem J 1988, 256(1):283-290. 1135400, 2851982.
39. Boudreau RT, Conrad DM, Hoskin DW. Apoptosis induced by protein phosphatase 2A (PP2A) inhibition in T leukemia cells is negatively regulated by PP2A-associated p38 mitogen-activated protein kinase. Cell Signal 2007, 19(1):139-151. 10.1016/j.cellsig.2006.05.030, 16844342.
40. Li W, Chen Z, Gong FR, Zong Y, Chen K, Li DM, Yin H, Duan WM, Miao Y, Tao M, Han X, Xu ZK. 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 2011, 47(17):2654-2664. 10.1016/j.ejca.2011.08.014, 21958460.
41. Hofstetter CP, Burkhardt JK, Shin BJ, Gursel DB, Mubita L, Gorrepati R, Brennan C, Holland EC, Boockvar JA. Protein phosphatase 2A mediates dormancy of glioblastoma multiforme-derived tumor stem-like cells during hypoxia. PLoS One 2012, 7(1):e30059. 10.1371/journal.pone.0030059, 3256196, 22253878.
42. Wong LL, Chang CF, Koay ES, Zhang D. Tyrosine phosphorylation of PP2A is regulated by HER-2 signalling and correlates with breast cancer progression. Int J Oncol 2009, 34(5):1291-1301.
43. Saddoughi SA, Gencer S, Peterson YK, Ward KE, Mukhopadhyay A, Oaks J, Bielawski J, Szulc ZM, Thomas RJ, Selvam SP, Senkal CE, Garrett-Mayer E, De Palma RM, Fedarovich D, Liu A, Habib AA, Stahelin RV, Perrotti D, Ogretmen B. Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis. EMBO Mol Med 2013, 5(1):105-121. 10.1002/emmm.201201283, 3569657, 23180565.
44. Lewy DS, Gauss CM, Soenen DR, Boger DL. Fostriecin: chemistry and biology. Curr Med Chem 2002, 9(22):2005-2032. 10.2174/0929867023368809, 12369868.
45. Zhang C, Peng Y, Wang F, Tan X, Liu N, Fan S, Wang D, Zhang L, Liu D, Wang T, Wang S, Zhou Y, Su Y, Cheng T, Zhuang Z, Shi C. A synthetic cantharidin analog for the enhancement of doxorubicin suppression of stem cell-derived aggressive sarcoma. Biomaterials 2010, 31(36):9535-9543. 10.1016/j.biomaterials.2010.08.059, 20875681.
46. Lu J, Zhuang Z, Song DK, Mehta GU, Ikejiri B, Mushlin H, Park DM, Lonser RR. The effect of a PP2A inhibitor on the nuclear receptor corepressor pathway in glioma. J Neurosurg 2010, 113(2):225-233. 10.3171/2009.11.JNS091272, 20001590.
47. Martiniova L, Lu J, Chiang J, Bernardo M, Lonser R, Zhuang Z, Pacak K. Pharmacologic modulation of serine/threonine phosphorylation highly sensitizes PHEO in a MPC cell and mouse model to conventional chemotherapy. PLoS One 2011, 6(2):e14678. 10.1371/journal.pone.0014678, 3038858, 21339823.
48. Lu J, Kovach JS, Johnson F, Chiang J, Hodes R, Lonser R, Zhuang Z. Inhibition of serine/threonine phosphatase PP2A enhances cancer chemotherapy by blocking DNA damage induced defense mechanisms. Proc Natl Acad Sci U S A 2009, 106(28):11697-11702. 10.1073/pnas.0905930106, 2710674, 19564615.
49. Mi H, Muruganujan A, Thomas PD. PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees. Nucl Acids Res 2013, 41(Database issue):D377-86.50. 3531194, 23193289.
50. Mi H, Thomas P. Protein networks and pathway analysis. Methods Mol Biol 2009, 563(2):123-140.