| Note | |
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| Entity | Mesothelioma |
| Disease | Various reports suggested that MetAP2 plays an important role in the growth of different types of tumors. Malignant mesothelioma cells expressed higher MetAP2 mRNA levels compared to normal mesothelioma cells (Catalano et al., 2001). Transfection of mesothelioma cells with a MetAP2 anti-sense oligonucleotide revealed a time-dependent inhibition of cell survival and induced nucleosome formation. MetAP2 is a main regulator of the proliferative and apoptotic pathways in mesothelioma cells and MetAP2 inhibition may represent a potential target for therapeutic intervention in human mesothelioma (Catalano et al., 2001). |
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| Entity | Lymphomas |
| Disease | A high level of MetAP2 was reported in malignant lymphomas exclusively in B-cell lymphoma subtypes (Kanno et al., 2002). |
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| Entity | Colorectal adenocarcinoma |
| Disease | It has been reported that a high expression of MetAP2 in colorectal adenocarcinoma patients (Selvakumar et al., 2004a). Since myristoylation reaction is catalyzed by NMT, we reported that a cross-talk among the MetAP2, and NMT in HT29 cells (Selvakumar et al., 2004b). The expression of pp60c-src, MetAP2, and NMT was dependent on the cell density (Selvakumar et al., 2004b). |
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| Entity | Esophageal squamous carcinoma |
| Disease | Microarray gene expression analysis of human esophageal squamous cell carcinomas revealed that MetAP2 was down-regulated when irradiated (Bo et al., 2004). |
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| Entity | Hepatoma |
| Disease | Anti-sense of MetAP2 also induces apoptosis in rat hepatoma cells (Datta and Datta, 1999). A recent study suggested that fumagillin effectively inhibits both liver tumor growth and metastasis in rats in vivo (Sheen et al., 2005). |
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| Entity | Neuroblastoma |
| Note | The angiogenesis inhibitor TNP470, O-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, suppressed the expression of MetAP2 in human neuroblastoma and thus, MetAP2 may be an important molecular target for human neuroblastomas (Morowitz et al., 2005). The intracellular enzyme MetAP2 became such a candidate target enzyme due to its inactivation by the widely investigated anticancer agent TNP470 (Abe et al., 1994; Adams et al., 2004; Griffith et al., 1997; Hu et et al., 2006; Hu et al., 2007; Sin et al., 1997). Previously, inhibition of MetAP2 by TNP470 has been shown to activate p53 for cell-cycle arrest. In fact, the primary mouse embryonic fibroblasts were demonstrated to be sensitive to TNP470 and other MetAP2-specific inhibitors in a p53-dependent fashion. Several MetAP2 inhibitors were studied based on the inhibition of MetAP activity (Griffith et al., 1998; Antoine et al., 1994; Kusaka et al., 1994; Wang et al., 2000; Wang et al., 2003; Yeh et al., 2000; Zhang et al., 2000; Kim et al., 2004; Towbin et al., 2003). |
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| Entity | Various cancer |
| Note | MetAP2 inhibitors
It has been reported that MetAP2 could function as an oncogene (Tucker et al., 2008). Furthermore, various Src family tyrosine kinases, ADP ribosylation factors and eukaryotic transcription elongation factor-2 were substrates of MetAP2 which plays a significant role in the progression of metastasis (Tucker et al., 2008). A derivative of the natural product fumagillin, TNP470 has been shown to be safe and effective in the treatment of solid tumors in several animal studies and preclinical trials. TNP470 entered human clinical trials for the treatment of AIDS-related Kaposi's sarcoma, metastatic breast cancer, androgen-independent prostate cancer, pediatric solid tumors, lymphomas, acute leukemia, advanced squamous cell cancer of the cervix, and metastatic renal carcinoma (Dezube et al., 1998; Kruger and Figg, 2000; Kudelka et al., 1997). Several MetAP2 inhibitors were studied based on the inhibition of MetAP activity (Griffith et al., 1998; Antoine et al., 1994; Kusaka et al., 1994; Wang et al., 2000; Yeh et al., 2000; Zhang et al., 2000; Kim et al., 2004). Previously, inhibition of MetAP2 by TNP470 has been shown to activate p53 for cell-cycle arrest (Yeh et al., 2000; Zhang et al., 2000).
The Src family kinases have been shown to play pivotal roles in cell-cycle progression, making them potential candidates to mediate the cell-cycle effects of MetAP inhibitors. MetAP2 plays a critical role in the proliferation of endothelial cells and certain tumor cells and thus serves as a promising target for anti-angiogenesis and anti-cancer drugs (Bo et al., 2004). The inhibition of MetAP2 expression in mesothelioma cells leads to cell death and that such apoptosis is avoided in cases where there is overexpression of Bcl-2 (Catalano et al., 2001). The upregulation of Bcl-2 in colorectal cancer is well established by various investigators (Rajala et al., 2000; Yu et al., 2003; Valassiadou et al., 1997). |
| | |
| A fumagillin derivative angiogenesis inhibitor, AGM-1470, inhibits activation of cyclin-dependent kinases and phosphorylation of retinoblastoma gene product but not protein tyrosyl phosphorylation or protooncogene expression in vascular endothelial cells. |
| Abe J, Zhou W, Takuwa N, Taguchi J, Kurokawa K, Kumada M, Takuwa Y. |
| Cancer Res. 1994 Jul 1;54(13):3407-12. |
| PMID 8012959 |
| |
| Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. |
| Adams BK, Ferstl EM, Davis MC, Herold M, Kurtkaya S, Camalier RF, Hollingshead MG, Kaur G, Sausville EA, Rickles FR, Snyder JP, Liotta DC, Shoji M. |
| Bioorg Med Chem. 2004 Jul 15;12(14):3871-83. |
| PMID 15210154 |
| |
| AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not transformed endothelial cells into the G1 phase of the cell cycle. |
| Antoine N, Greimers R, De Roanne C, Kusaka M, Heinen E, Simar LJ, Castronovo V. |
| Cancer Res. 1994 Apr 15;54(8):2073-6. |
| PMID 7513609 |
| |
| Effect of ionizing irradiation on human esophageal cancer cell lines by cDNA microarray gene expression analysis. |
| Bo H, Ghazizadeh M, Shimizu H, Kurihara Y, Egawa S, Moriyama Y, Tajiri T, Kawanami O. |
| J Nippon Med Sch. 2004 Jun;71(3):172-80. |
| PMID 15226608 |
| |
| N-terminal processing: the methionine aminopeptidase and N alpha-acetyl transferase families. |
| Bradshaw RA, Brickey WW, Walker KW. |
| Trends Biochem Sci. 1998 Jul;23(7):263-7. (REVIEW) |
| PMID 9697417 |
| |
| Methionine aminopeptidase-2 regulates human mesothelioma cell survival: role of Bcl-2 expression and telomerase activity. |
| Catalano A, Romano M, Robuffo I, Strizzi L, Procopio A. |
| Am J Pathol. 2001 Aug;159(2):721-31. |
| PMID 11485930 |
| |
| Induction of apoptosis due to lowering the level of eukaryotic initiation factor 2-associated protein, p67, from mammalian cells by antisense approach. |
| Datta B, Datta R. |
| Exp Cell Res. 1999 Feb 1;246(2):376-83. |
| PMID 9925753 |
| |
| Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical Trial Group study. AIDS Clinical Trial Group No. 215 Team. |
| Dezube BJ, Von Roenn JH, Holden-Wiltse J, Cheung TW, Remick SC, Cooley TP, Moore J, Sommadossi JP, Shriver SL, Suckow CW, Gill PS. |
| J Clin Oncol. 1998 Apr;16(4):1444-9. |
| PMID 9552050 |
| |
| Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2. |
| Griffith EC, Su Z, Niwayama S, Ramsay CA, Chang YH, Liu JO. |
| Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15183-8. |
| PMID 9860943 |
| |
| Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression. |
| Hu X, Addlagatta A, Lu J, Matthews BW, Liu JO. |
| Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18148-53. Epub 2006 Nov 17. |
| PMID 17114291 |
| |
| Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases. |
| Hu X, Dang Y, Tenney K, Crews P, Tsai CW, Sixt KM, Cole PA, Liu JO. |
| Chem Biol. 2007 Jul;14(7):764-74. |
| PMID 17656313 |
| |
| Role of methionine in the initiation of haemoglobin synthesis. |
| Jackson R, Hunter T. |
| Nature. 1970 Aug 15;227(5259):672-6. |
| PMID 5432061 |
| |
| High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts. |
| Kanno T, Endo H, Takeuchi K, Morishita Y, Fukayama M, Mori S. |
| Lab Invest. 2002 Jul;82(7):893-901. |
| PMID 12118091 |
| |
| Depletion of methionine aminopeptidase 2 does not alter cell response to fumagillin or bengamides. |
| Kim S, LaMontagne K, Sabio M, Sharma S, Versace RW, Yusuff N, Phillips PE. |
| Cancer Res. 2004 May 1;64(9):2984-7. |
| PMID 15126329 |
| |
| TNP-470: an angiogenesis inhibitor in clinical development for cancer. |
| Kruger EA, Figg WD. |
| Expert Opin Investig Drugs. 2000 Jun;9(6):1383-96. (REVIEW) |
| PMID 11060750 |
| |
| A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. |
| Kudelka AP, Levy T, Verschraegen CF, Edwards CL, Piamsomboon S, Termrungruanglert W, Freedman RS, Kaplan AL, Kieback DG, Meyers CA, Jaeckle KA, Loyer E, Steger M, Mante R, Mavligit G, Killian A, Tang RA, Gutterman JU, Kavanagh JJ. |
| Clin Cancer Res. 1997 Sep;3(9):1501-5. |
| PMID 9815836 |
| |
| Cytostatic inhibition of endothelial cell growth by the angiogenesis inhibitor TNP-470 (AGM-1470). |
| Kusaka M, Sudo K, Matsutani E, Kozai Y, Marui S, Fujita T, Ingber D, Folkman J. |
| Br J Cancer. 1994 Feb;69(2):212-6. |
| PMID 8297716 |
| |
| Methionine aminopeptidase 2 inhibition is an effective treatment strategy for neuroblastoma in preclinical models. |
| Morowitz MJ, Barr R, Wang Q, King R, Rhodin N, Pawel B, Zhao H, Erickson SA, Sheppard GS, Wang J, Maris JM, Shusterman S. |
| Clin Cancer Res. 2005 Apr 1;11(7):2680-5. |
| PMID 15814649 |
| |
| Increased expression of N-myristoyltransferase in gallbladder carcinomas. |
| Rajala RV, Radhi JM, Kakkar R, Datla RS, Sharma RK. |
| Cancer. 2000 May 1;88(9):1992-9. |
| PMID 10813869 |
| |
| Potential role of N-myristoyltransferase in cancer. |
| Selvakumar P, Lakshmikuttyamma A, Shrivastav A, Das SB, Dimmock JR, Sharma RK. |
| Prog Lipid Res. 2007 Jan;46(1):1-36. Epub 2006 Jun 12. (REVIEW) |
| PMID 16846646 |
| |
| Fumagillin treatment of hepatocellular carcinoma in rats: an in vivo study of antiangiogenesis. |
| Sheen IS, Jeng KS, Jeng WJ, Jeng CJ, Wang YC, Gu SL, Tseng SY, Chu CM, Lin CH, Chang KM. |
| World J Gastroenterol. 2005 Feb 14;11(6):771-7. |
| PMID 15682466 |
| |
| The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. |
| Sin N, Meng L, Wang MQ, Wen JJ, Bornmann WG, Crews CM. |
| Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6099-103. |
| PMID 9177176 |
| |
| Processing of the N termini of nascent polypeptide chains requires deformylation prior to methionine removal. |
| Solbiati J, Chapman-Smith A, Miller JL, Miller CG, Cronan JE Jr. |
| J Mol Biol. 1999 Jul 16;290(3):607-14. |
| PMID 10395817 |
| |
| Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors. |
| Towbin H, Bair KW, DeCaprio JA, Eck MJ, Kim S, Kinder FR, Morollo A, Mueller DR, Schindler P, Song HK, van Oostrum J, Versace RW, Voshol H, Wood J, Zabludoff S, Phillips PE. |
| J Biol Chem. 2003 Dec 26;278(52):52964-71. Epub 2003 Oct 8. |
| PMID 14534293 |
| |
| Ectopic expression of methionine aminopeptidase-2 causes cell transformation and stimulates proliferation. |
| Tucker LA, Zhang Q, Sheppard GS, Lou P, Jiang F, McKeegan E, Lesniewski R, Davidsen SK, Bell RL, Wang J. |
| Oncogene. 2008 Jun 26;27(28):3967-76. Epub 2008 Feb 11. |
| PMID 18264137 |
| |
| Immunohistochemical expression of p53, bcl-2, mdm2 and waf1/p21 proteins in colorectal adenocarcinomas. |
| Valassiadou KE, Stefanaki K, Tzardi M, Datseris G, Georgoulias V, Melissas J, Tsiftsis DD, Delides G, Kanavaros P. |
| Anticancer Res. 1997 Jul-Aug;17(4A):2571-6. |
| PMID 9252682 |
| |
| Selective inhibition of endothelial cell proliferation by fumagillin is not due to differential expression of methionine aminopeptidases. |
| Wang J, Lou P, Henkin J. |
| J Cell Biochem. 2000 Apr;77(3):465-73. |
| PMID 10760954 |
| |
| Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2. |
| Wang J, Sheppard GS, Lou P, Kawai M, BaMaung N, Erickson SA, Tucker-Garcia L, Park C, Bouska J, Wang YC, Frost D, Tapang P, Albert DH, Morgan SJ, Morowitz M, Shusterman S, Maris JM, Lesniewski R, Henkin J. |
| Cancer Res. 2003 Nov 15;63(22):7861-9. |
| PMID 14633714 |
| |
| The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest. |
| Yeh JR, Mohan R, Crews CM. |
| Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12782-7. |
| PMID 11070090 |
| |
| Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21WAF1/CIP1. |
| Zhang Y, Griffith EC, Sage J, Jacks T, Liu JO. |
| Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6427-32. |
| PMID 10841547 |
| |
