Table of Contents
Journal of Cancer Research
Volume 2014 (2014), Article ID 423401, 12 pages
http://dx.doi.org/10.1155/2014/423401
Review Article

A Review of the Potential Utility of Mycophenolate Mofetil as a Cancer Therapeutic

1Department of Neurology, University of Cincinnati Medical Center, 260 Stetson Street, Suite 2300, Cincinnati, OH 45267-0525, USA
2Division of Hematology-Oncology, Department of Internal Medicine, UC Cancer Institute, 3125 Eden Avenue Room 2112, Mail Loc-0562, Cincinnati, OH 45221, USA
3Department of Neurosurgery, UC Brain Tumor Center, 260 Stetson Street, Mail Loc-0515, Cincinnati, OH 45221, USA
4Department of Reproductive Medicine, Cincinnati Children’s Hospital Medical Center, Mail Loc-0054, Cincinnati, OH 45221, USA
5Department of Radiation Oncology, Trihealth Cancer Institute, 4415 Aicholtz Road, Cincinnati, OH 45245, USA
6Vontz Center for Molecular Studies, 3125 Eden Avenue Room 2112, Cincinnati, OH 45221, USA

Received 20 January 2014; Revised 18 March 2014; Accepted 21 March 2014; Published 7 July 2014

Academic Editor: Takahiro Yamauchi

Copyright © 2014 Nazanin Majd et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Liu, H. Cheng, T. M. Roberts, and J. J. Zhao, “Targeting the phosphoinositide 3-kinase pathway in cancer,” Nature Reviews Drug Discovery, vol. 8, no. 8, pp. 627–644, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. R. A. Cairns, I. S. Harris, and T. W. Mak, “Regulation of cancer cell metabolism,” Nature Reviews Cancer, vol. 11, no. 2, pp. 85–95, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. K. H. Khan, T. A. Yap, L. Yan, and D. Cunningham, “Targeting the PI3K-AKT-mTOR signaling network in cancer,” Chinese Journal of Cancer, vol. 32, no. 5, pp. 253–265, 2013. View at Publisher · View at Google Scholar
  4. J. S. Carew, K. R. Kelly, and S. T. Nawrocki, “Mechanisms of mTOR inhibitor resistance in cancer therapy,” Targeted Oncology, vol. 6, no. 1, pp. 17–27, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. T. W. Traut, “Physiological concentrations of purines and pyrimidines,” Molecular and Cellular Biochemistry, vol. 140, no. 1, pp. 1–22, 1994. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. Natsumeda, N. Prajda, J. P. Donohue, J. L. Glover, and G. Weber, “Enzymic capacities of purine de novo and salvage pathways for nucleotide synthesis in normal and neoplastic tissues,” Cancer Research, vol. 44, no. 6, pp. 2475–2479, 1984. View at Google Scholar · View at Scopus
  7. X. Tong, F. Zhao, and C. B. Thompson, “The molecular determinants of de novo nucleotide biosynthesis in cancer cells,” Current Opinion in Genetics & Development, vol. 19, no. 1, pp. 32–37, 2009. View at Publisher · View at Google Scholar
  8. Y. Natsumeda, S. Ohno, H. Kawasaki, Y. Konno, G. Weber, and K. Suzuki, “Two distinct cDNAs for human IMP dehydrogenase,” The Journal of Biological Chemistry, vol. 265, no. 9, pp. 5292–5295, 1990. View at Google Scholar · View at Scopus
  9. J. Fellenberg, P. Kunz, H. Sähr, and D. Depeweg, “Overexpression of inosine 5’-monophosphate dehydrogenase type II mediates chemoresistance to human osteosarcoma cells,” PLoS ONE, vol. 5, no. 8, Article ID e12179, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. C. Brouwer, D. G. M. Vermunt-de Koning, R. C. Trueworthy et al., “Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: enzymological and clinical aspects,” Pediatric Blood and Cancer, vol. 46, no. 4, pp. 434–438, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Jain, S. J. Almquist, P. J. Ford et al., “Regulation of inosine monophosphate dehydrogenase type I and type II isoforms in human lymphocytes,” Biochemical Pharmacology, vol. 67, no. 4, pp. 767–776, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. S. J. Bowne, Q. Liu, L. S. Sullivan et al., “Why do mutations in the ubiquitously expressed housekeeping gene IMPDH1 cause retina-specific photoreceptor degeneration?” Investigative Ophthalmology and Visual Science, vol. 47, no. 9, pp. 3754–3765, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Fellenberg, L. Bernd, G. Delling, D. Witte, and A. Zahlten-Hinguranage, “Prognostic significance of drug-regulated genes in high-grade osteosarcoma,” Modern Pathology, vol. 20, no. 10, pp. 1085–1094, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Peñuelas, V. Noé, and C. J. Ciudad, “Modulation of IMPDH2, survivin, topoisomerase I and vimentin increases sensitivity to methotrexate in HT29 human colon cancer cells,” FEBS Journal, vol. 272, no. 3, pp. 696–710, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Peñuelas, V. Noé, R. Morales, and C. J. Ciudad, “Sensitization of human erythroleukemia K562 cells resistant to methotrexate by inhibiting IMPDH,” Medical Science Monitor, vol. 11, no. 1, pp. BR6–BR12, 2005. View at Google Scholar · View at Scopus
  16. M. Nagai, Y. Natsumeda, and G. Weber, “Proliferation-linked regulation of type II IMP dehydrogenase gene in human normal lymphocytes and HL-60 leukemic cells,” Cancer Research, vol. 52, no. 2, pp. 258–261, 1992. View at Google Scholar · View at Scopus
  17. M. Nagai, Y. Natsumeda, Y. Konno, R. Hoffman, S. Irino, and G. Weber, “Selective up-regulation of type II inosine 5′-monophosphate dehydrogenase messenger RNA expression in human leukemias,” Cancer Research, vol. 51, no. 15, pp. 3886–3890, 1991. View at Google Scholar · View at Scopus
  18. M. Escobar-Henriques, A. Balguerie, C. Monribot, H. Boucherie, and B. Daignan-Fornier, “Proteome analysis and morphological studies reveal multiple effects of the immunosuppressive drug mycophenolic acid specifically resulting from guanylic nucleotide depletion,” The Journal of Biological Chemistry, vol. 276, no. 49, pp. 46237–46242, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. J. N. Kuehner and D. A. Brow, “Regulation of a eukaryotic gene by GTP-dependent start site selection and transcription attenuation,” Molecular Cell, vol. 31, no. 2, pp. 201–211, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. K. Pillwein, P. Chiba, A. Knoflach et al., “Purine metabolism of human glioblastoma in vivo,” Cancer Research, vol. 50, no. 5, pp. 1576–1579, 1990. View at Google Scholar · View at Scopus
  21. H. N. Jayaram, D. A. Cooney, M. Grusch, and G. Krupitza, “Consequences of IMP dehydrogenase inhibition, and its relationship to cancer and apoptosis,” Current Medicinal Chemistry, vol. 6, no. 7, pp. 561–574, 1999. View at Google Scholar · View at Scopus
  22. K. Gharehbaghi, G. S. Burgess, F. R. Collart et al., “P210 Bcr-Abl confers overexpression of inosine monophosphate dehydrogenase: an intrinsic pathway to drug resistance mediated by oncogene,” Leukemia, vol. 8, no. 8, pp. 1257–1263, 1994. View at Google Scholar · View at Scopus
  23. R. Bullingham, S. Monroe, A. Nicholls, and M. Hale, “Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration,” Journal of Clinical Pharmacology, vol. 36, no. 4, pp. 315–324, 1996. View at Google Scholar · View at Scopus
  24. R. A. Moore and S. Derry, “Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis,” Arthritis Research and Therapy, vol. 8, article R182, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. J. Zwerner and D. Fiorentino, “Mycophenolate mofetil,” Dermatologic Therapy, vol. 20, no. 4, pp. 229–238, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Suzuki, T. Kimura, K. Ando, M. Sawada, and G. Tamura, “Antitumor activity of mycophenolic acid,” Journal of Antibiotics, vol. 22, no. 7, pp. 297–302, 1969. View at Google Scholar · View at Scopus
  27. R. J. Tressler, L. J. Garvin, and D. L. Slate, “Anti-tumour activity of mycophenolate mofetil against human and mouse tumors in vivo,” International Journal of Cancer, vol. 57, no. 4, pp. 568–573, 1994. View at Publisher · View at Google Scholar · View at Scopus
  28. D. Floryk and E. Huberman, “Mycophenolic acid-induced replication arrest, differentiation markers and cell death of androgen-independent prostate cancer cells DU145,” Cancer Letters, vol. 231, no. 1, pp. 20–29, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. E. Messina, L. Barile, F. Lupi, and A. Giacomello, “Potential role of mycophenolate mofetil in the management of neuroblastoma patients,” Nucleosides, Nucleotides and Nucleic Acids, vol. 23, no. 8-9, pp. 1545–1549, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. N. Takebe, X. Cheng, T. E. Fandy et al., “IMP dehydrogenase inhibitor mycophenolate mofetil induces caspase-dependent apoptosis and cell cycle inhibition in multiple myeloma cells,” Molecular Cancer Therapeutics, vol. 5, no. 2, pp. 457–466, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. C. Drullion, V. Lagarde, R. Gioia et al., “Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest,” Leukemia Research and Treatment, vol. 2012, Article ID 861301, 9 pages, 2012. View at Publisher · View at Google Scholar
  32. Z.-H. Zheng, Y. Yang, X.-H. Lu et al., “Mycophenolic acid induces adipocyte-like differentiation and reversal of malignancy of breast cancer cells partly through PPARγ,” European Journal of Pharmacology, vol. 658, no. 1, pp. 1–8, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. G. E. Koehl, F. Wagner, O. Stoeltzing et al., “Mycophenolate mofetil inhibits tumor growth and angiogenesis in vitro but has variable antitumor effects in vivo, possibly related to bioavailability,” Transplantation, vol. 83, no. 5, pp. 607–614, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Engl, J. Makarević, B. Relja et al., “Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy,” BMC Cancer, vol. 5, article 4, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. K. Leckel, W.-D. Beecken, D. Jonas et al., “The immunosuppressive drug mycophenolate mofetil impairs the adhesion capacity of gastrointestinal tumour cells,” Clinical and Experimental Immunology, vol. 134, no. 2, pp. 238–245, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Domhan, S. Muschal, C. Schwager et al., “Molecular mechanisms of the antiangiogenic and antitumor effects of mycophenolic acid,” Molecular Cancer Therapeutics, vol. 7, no. 6, pp. 1656–1668, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. P. Tuncyurek, J. M. Mayer, F. Klug et al., “Everolimus and mycophenolate mofetil sensitize human pancreatic cancer cells to gemcitabine in vitro: a novel adjunct to standard chemotherapy?” European Surgical Research, vol. 39, no. 6, pp. 380–387, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. C. R. Chong, D. Z. Qian, F. Pan et al., “Identification of type 1 inosine monophosphate dehydrogenase as an antiangiogenic drug target,” Journal of Medicinal Chemistry, vol. 49, no. 9, pp. 2677–2680, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. A. C. Allison and E. M. Eugui, “Mycophenolate mofetil and its mechanisms of action,” Immunopharmacology, vol. 47, no. 2-3, pp. 85–118, 2000. View at Publisher · View at Google Scholar · View at Scopus
  40. R. A. Blaheta, H. Bogossian, W.-D. Beecken et al., “Mycophenolate mofetil increases adhesion capacity of tumor cells in vitro,” Transplantation, vol. 76, no. 12, pp. 1735–1741, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. U. Heemann, H. Azuma, P. Hamar, C. Schmid, N. Tilney, and T. Philipp, “Mycophenolate mofetil inhibits lymphocyte binding and the upregulation of adhesion molecules in acute rejection of rat kidney allografts,” Transplant Immunology, vol. 4, no. 1, pp. 64–67, 1996. View at Publisher · View at Google Scholar · View at Scopus
  42. B. Dun, A. Sharma, Y. Teng et al., “Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways,” PLoS ONE, vol. 8, Article ID e81702, 2013. View at Publisher · View at Google Scholar
  43. Y. Shintani, M. A. Hollingsworth, M. J. Wheelock, and K. R. Johnson, “Collagen I promotes metastasis in pancreatic cancer by activating c-Jun NH2-terminal kinase 1 and up-regulating N-cadherin expression,” Cancer Research, vol. 66, no. 24, pp. 11745–11753, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. N. Takebe, X. Cheng, S. Wu et al., “Phase I clinical trial of the inosine monophosphate dehydrogenase inhibitor mycophenolate mofetil (Cellcept) in advanced multiple myeloma patients,” Clinical Cancer Research, vol. 10, no. 24, pp. 8301–8308, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. J. Rodríguez-Pascual, P. Sha, E. García-García et al., “A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer,” Investigational New Drugs, vol. 31, no. 1, pp. 14–19, 2013. View at Publisher · View at Google Scholar
  46. B. C. M. de Winter, R. A. A. Mathot, F. Sombogaard, A. G. Vulto, and T. van Gelder, “Nonlinear relationship between mycophenolate mofetil dose and mycophenolic acid exposure: implications for therapeutic drug monitoring,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 3, pp. 656–663, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. W. A. Lee, L. Gu, A. R. Miksztal, N. Chu, K. Leung, and P. H. Nelson, “Bioavailability improvement of mycophenolic acid through amino ester derivatization,” Pharmaceutical Research, vol. 7, no. 2, pp. 161–166, 1990. View at Publisher · View at Google Scholar · View at Scopus
  48. P. Reinke, K. Budde, C. Hugo et al., “Reduction of gastrointestinal complications in renal graft recipients after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium,” Transplantation Proceedings, vol. 43, no. 5, pp. 1641–1646, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. F. Ortega, A. Sánchez-Fructuoso, J. M. Cruzado et al., “Gastrointestinal quality of life improvement of renal transplant recipients converted from mycophenolate mofetil to enteric-coated mycophenolate sodium drugs or agents: mycophenolate mofetil and enteric-coated mycophenolate sodium,” Transplantation, vol. 92, no. 4, pp. 426–432, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. D. K. Granger, “Enteric-coated mycophenolate sodium: results of two pivotal global multicenter trials,” Transplantation Proceedings, vol. 33, no. 7-8, pp. 3241–3244, 2001. View at Publisher · View at Google Scholar · View at Scopus
  51. C. E. Staatz and S. E. Tett, “Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients,” Clinical Pharmacokinetics, vol. 46, no. 1, pp. 13–58, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. M. D. Pescovitz, D. Conti, J. Dunn et al., “Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics,” Clinical Transplantation, vol. 14, no. 3, pp. 179–188, 2000. View at Publisher · View at Google Scholar · View at Scopus
  53. B. A. Atcheson, P. J. Taylor, C. M. J. Kirkpatrick et al., “Free mycophenolic acid should be monitored in renal transplant recipients with hypoalbuminemia,” Therapeutic Drug Monitoring, vol. 26, no. 3, pp. 284–286, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. B. Kaplan, H. U. Meier-Kriesche, G. Friedman et al., “The effect of renal insufficiency on mycophenolic acid protein binding,” Journal of Clinical Pharmacology, vol. 39, no. 7, pp. 715–720, 1999. View at Publisher · View at Google Scholar · View at Scopus
  55. H.-U. Meier-Kriesche, L. M. Shaw, M. Korecka, and B. Kaplan, “Pharmacokinetics of mycophenolic acid in renal insufficiency,” Therapeutic Drug Monitoring, vol. 22, no. 1, pp. 27–30, 2000. View at Publisher · View at Google Scholar · View at Scopus
  56. J. F. Buell, T. G. Gross, and E. S. Woodle, “Malignancy after transplantation,” Transplantation, vol. 80, no. 2, pp. S254–S264, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. S. B. Campbell, R. Walker, S. S. Tai, Q. Jiang, and G. R. Russ, “Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer,” American Journal of Transplantation, vol. 12, no. 5, pp. 1146–1156, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Robson, J. M. Cecka, G. Opelz, M. Budde, and S. Sacks, “Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil,” American Journal of Transplantation, vol. 5, no. 12, pp. 2954–2960, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. J. O. O’Neill, L. B. Edwards, and D. O. Taylor, “Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation,” Journal of Heart and Lung Transplantation, vol. 25, no. 10, pp. 1186–1191, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. P. Braconnier, V. del Marmol, N. Broeders et al., “Combined introduction of anti-IL2 receptor antibodies, mycophenolic acid and tacrolimus: effect on malignancies after renal transplantation in a single-centre retrospective cohort study,” Nephrology Dialysis Transplantation, vol. 27, no. 6, pp. 2547–2553, 2012. View at Publisher · View at Google Scholar
  61. J. R. Lake, K. M. David, B. J. Steffen, A. H. Chu, R. D. Gordon, and R. H. Wiesner, “Addition of MMF to dual immunosuppression does not increase the risk of malignant short-term death after liver transplantation,” American Journal of Transplantation, vol. 5, no. 12, pp. 2961–2967, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Vernino, D. R. Salomao, T. M. Habermann, and B. P. O’Neill, “Primary CNS lymphoma complicating treatment of myasthenia gravis with mycophenolate mofetil,” Neurology, vol. 65, no. 4, pp. 639–641, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. N. Dasgupta, A. C. Gelber, F. Racke, and D. M. Fine, “Central nervous system lymphoma associated with mycophenolate mofetil in lupus nephritis,” Lupus, vol. 14, no. 11, pp. 910–913, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. P. F. Finelli, K. Naik, J. A. DiGiuseppe, and A. Prasad, “Primary lymphoma of CNS, mycophenolate mofetil and lupus,” Lupus, vol. 15, no. 12, pp. 886–888, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. B. P. O’Neill, S. Vernino, A. Dogan, and C. Giannini, “EBV-associated lymphoproliferative disorder of CNS associated with the use of mycophenolate mofetil,” Neuro-Oncology, vol. 9, no. 3, pp. 364–369, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. G. Gebeyehu, V. E. Marquez, A. van Cott et al., “Ribavirin, tiazofurin, and selenazofurin: mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase,” Journal of Medicinal Chemistry, vol. 28, no. 1, pp. 99–105, 1985. View at Google Scholar · View at Scopus
  67. E. Olah, Y. Natsumeda, T. Ikegami et al., “Induction of erythroid differentiation and modulation of gene expression by tiazofurin in K-562 leukemia cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 17, pp. 6533–6537, 1988. View at Google Scholar · View at Scopus
  68. G. J. Tricot, H. N. Jayaram, E. Lapis et al., “Biochemically directed therapy of leukemia with tiazofurin, a selective blocker of inosine 5’-phosphate dehydrogenase activity,” Cancer Research, vol. 49, no. 13, pp. 3696–3701, 1989. View at Google Scholar · View at Scopus
  69. K. Malek, M. S. Boosalis, K. Waraska, B. S. Mitchell, and D. G. Wright, “Effects of the IMP-dehydrogenase inhibitor, Tiazofurin, in bcr-abl positive acute myelogenous leukemia—part I: in vivo studies,” Leukemia Research, vol. 28, no. 11, pp. 1125–1136, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. N. Khanna, H. N. Jayaram, and N. Singh, “Benzamide riboside induced mitochondrial mediated apoptosis in human lung cancer H520 cells,” Life Sciences, vol. 75, no. 2, pp. 179–190, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. D. Floryk and T. C. Thompson, “Antiproliferative effects of AVN944, a novel inosine 5-monophosphate dehydrogenase inhibitor, in prostate cancer cells,” International Journal of Cancer, vol. 123, no. 10, pp. 2294–2302, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. J. M. Hamilton, M. W. Harding, T. Genna, and D. K. Bol, “A phase I dose-ranging study of the pharmacokinetics, pharmacodynamics, safety, and tolerability of AVN944, an IMPDH inhibitor, in healthy male volunteers,” Journal of Clinical Pharmacology, vol. 49, no. 1, pp. 30–38, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. K. Ishitsuka, T. Hideshima, M. Hamasaki et al., “Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway,” Oncogene, vol. 24, no. 38, pp. 5888–5896, 2005. View at Publisher · View at Google Scholar · View at Scopus