Advertisement

Surgery Today

, Volume 41, Issue 2, pp 175–182 | Cite as

Inhibitor of apoptosis protein family as diagnostic markers and therapeutic targets of colorectal cancer

  • Koh Miura
  • Wataru Fujibuchi
  • Kazuyuki Ishida
  • Takeshi Naitoh
  • Hitoshi Ogawa
  • Toshinori Ando
  • Nobuki Yazaki
  • Kazuhiro Watanabe
  • Sho Haneda
  • Chikashi Shibata
  • Iwao Sasaki
Review Article

Abstract

The apoptosis and antiapoptotic signaling pathways are important for regulating carcinogenesis and cancer progression, and for determining prognosis. Molecules involved in apoptosis represent potential cancer diagnostic markers and therapeutic targets. The inhibitor of apoptosis protein (IAP) family includes several important molecules involved in apoptosis that might represent such targets. Increasing evidence has demonstrated that the IAP family of proteins is integral for antiapoptotic and nuclear factor-κB signal transduction, and enhanced expression of IAPs contributes to colon carcinogenesis and its poor prognosis, as well as to drug resistance of tumors. X-linked IAP, cIAP1, cIAP2, and survivin are prognostic markers of colorectal cancer, and survivin and cIAP2 are also utilized to predict the effect of anticancer treatment in colorectal cancer patients. Novel therapies such as YM155 and LY2181308 targeting survivin, AEG35156 and phenoxodiol targeting X-linked IAP, AT-406 as a Smac mimetic, and survivin peptides are currently being evaluated in clinical trials. This report reviews the involvement of the IAP family in colorectal adenocarcinoma in order to summarize the role of the IAP family members as diagnostic and therapeutic targets, and to provide an overview of the future course of research in this area.

Key words

Inhibitor of apoptosis protein family Colorectal cancer Diagnostic marker Therapeutic target Clinical trial 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med 2005;352:476–487.CrossRefPubMedGoogle Scholar
  3. 3.
    Bedi A, Pasricha PJ, Akhtar AJ, Barber JP, Bedi GC, Giardiello FM, et al. Inhibition of apoptosis during development of colorectal cancer. Cancer Res 1995;55:1811–1816.PubMedGoogle Scholar
  4. 4.
    Hunter AM, LaCasse EC, Korneluk RG. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis 2007;12:1543–1568.CrossRefPubMedGoogle Scholar
  5. 5.
    Hinds MG, Norton RS, Vaux DL, Day CL. Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat. Nat Struct Biol 1999;6:648–651.CrossRefPubMedGoogle Scholar
  6. 6.
    Sun C, Cai M, Gunasekera AH, Meadows RP, Wang H, Chen J, et al. NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Nature 1999;401:818–822.CrossRefPubMedGoogle Scholar
  7. 7.
    Martin SJ. Dealing the CARDs between life and death. Trends Cell Biol 2001;11:188–189.CrossRefPubMedGoogle Scholar
  8. 8.
    Gyrd-Hansen M, Darding M, Miasari M, Santoro MM, Zender L, Xue W, et al. IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis. Nat Cell Biol 2008;10:1309–1317.CrossRefPubMedGoogle Scholar
  9. 9.
    Vischioni B, van der Valk P, Span SW, Kruyt FA, Rodriguez JA, Giaccone G. Expression and localization of inhibitor of apoptosis proteins in normal human tissues. Hum Pathol 2006;37:78–86.CrossRefPubMedGoogle Scholar
  10. 10.
    Ponnelle T, Chapusot C, Martin L, Bonithon-Kopp C, Bouvier AM, Plenchette S, et al. Subcellular expression of c-IAP1 and c-IAP2 in colorectal cancers: relationships with clinicopathological features and prognosis. Pathol Res Pract 2003;199:723–731.CrossRefPubMedGoogle Scholar
  11. 11.
    Endo T, Abe S, Seidlar HB, Nagaoka S, Takemura T, Utsuyama M, et al. Expression of IAP family proteins in colon cancers from patients with different age groups. Cancer Immunol Immunother 2004;53:770–776.CrossRefPubMedGoogle Scholar
  12. 12.
    Tamm I, Kornblau SM, Segall H, Krajewski S, Welsh K, Kitada S, et al. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 2000;6:1796–1803.PubMedGoogle Scholar
  13. 13.
    Qi G, Tuncel H, Aoki E, Tanaka S, Oka S, Kaneko I, et al. Intracellular localization of survivin determines biological behavior in colorectal cancer. Oncol Rep 2009;22:557–562.PubMedGoogle Scholar
  14. 14.
    Chang HY, Yang X. Proteases for cell suicide: functions and regulation of caspases. Microbiol Mol Biol Rev 2000;64:821–846.CrossRefPubMedGoogle Scholar
  15. 15.
    Fuentes-Prior P, Salvesen GS. The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J 2004;384:201–232.CrossRefPubMedGoogle Scholar
  16. 16.
    Adrain C, Martin SJ. The mitochondrial apoptosome: a killer unleashed by the cytochrome seas. Trends Biochem Sci 2001;26:390–397.CrossRefPubMedGoogle Scholar
  17. 17.
    Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, et al. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 1998;17:2215–2223.CrossRefPubMedGoogle Scholar
  18. 18.
    Karasawa H, Miura K, Fujibuchi W, Ishida K, Kaneko N, Kinouchi M, et al. Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells. Cancer Sci 2009;100:903–913.CrossRefPubMedGoogle Scholar
  19. 19.
    Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000;102:33–42.CrossRefPubMedGoogle Scholar
  20. 20.
    Santoro MM, Samuel T, Mitchell T, Reed JC, Stainier DY. Birc2 (cIap1) regulates endothelial cell integrity and blood vessel homeostasis. Nat Genet 2007;39:1397–1402.CrossRefPubMedGoogle Scholar
  21. 21.
    Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 2007;131:669–681.CrossRefPubMedGoogle Scholar
  22. 22.
    Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 1995;83:1243–1252.CrossRefPubMedGoogle Scholar
  23. 23.
    Dejardin E. The alternative NF-kappaB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem Pharmacol 2006;72:1161–1179.CrossRefPubMedGoogle Scholar
  24. 24.
    Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997;3:917–921.CrossRefPubMedGoogle Scholar
  25. 25.
    Vucic D, Fairbrother WJ. The inhibitor of apoptosis proteins as therapeutic targets in cancer. Clin Cancer Res 2007;13:5995–6000.CrossRefPubMedGoogle Scholar
  26. 26.
    Fang YJ, Lu ZH, Wang GQ, Pan ZZ, Zhou ZW, Yun JP, et al. Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. Int J Colorectal Dis 2009;24:875–884.CrossRefPubMedGoogle Scholar
  27. 27.
    Lee YY, Yu CP, Lin CK, Nieh S, Hsu KF, Chiang H, et al. Expression of survivin and cortactin in colorectal adenocarcinoma: association with clinicopathological parameters. Dis Markers 2009;26:9–18.PubMedGoogle Scholar
  28. 28.
    Søreide K, Gudlaugsson E, Skaland I, Janssen EA, Van Diermen B, Körner H, et al. Metachronous cancer development in patients with sporadic colorectal adenomas — multivariate risk model with independent and combined value of hTERT and survivin. Int J Colorectal Dis 2008;23:389–400.CrossRefPubMedGoogle Scholar
  29. 29.
    Sarela AI, Scott N, Ramsdale J, Markham AF, Guillou PJ. Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomas. Ann Surg Oncol 2001;8:305–310.CrossRefPubMedGoogle Scholar
  30. 30.
    Xiang G, Wen X, Wang H, Chen K, Liu H. Expression of X-linked inhibitor of apoptosis protein in human colorectal cancer and its correlation with prognosis. J Surg Oncol 2009;100:708–712.CrossRefPubMedGoogle Scholar
  31. 31.
    De Oliveira Lima F, De Oliveira Costa H, Barrezueta LF, Fujiyama Oshima CT, Silva JA Jr, Gomes TS, et al. Immunoexpression of inhibitors of apoptosis proteins and their antagonist SMAC/DIABLO in colorectal carcinoma: correlation with apoptotic index, cellular proliferation and prognosis. Oncol Rep 2009;22:295–303.PubMedGoogle Scholar
  32. 32.
    Krajewska M, Kim H, Kim C, Kang H, Welsh K, Matsuzawa S, et al. Analysis of apoptosis protein expression in early-stage colorectal cancer suggests opportunities for new apoptotic biomarkers. Clin Cancer Res 2005;11:5451–5461.CrossRefPubMedGoogle Scholar
  33. 33.
    Lassmann S, Tang L, Capanu M, Brabletz T, Schöpflin A, Zur Hausen A, et al. Predictive molecular markers for colorectal cancer patients with resected liver metastasis and adjuvant chemotherapy. Gastroenterology 2007;133:1831–1839.CrossRefPubMedGoogle Scholar
  34. 34.
    Terzi C, Canda AE, Sagol O, Atila K, Sonmez D, Fuzun M, et al. Survivin, p53, and Ki-67 as predictors of histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Int J Colorectal Dis 2008;23:37–45.CrossRefPubMedGoogle Scholar
  35. 35.
    McDowell DT, Smith FM, Reynolds JV, Maher SG, Adida C, Crotty P, et al. Increased spontaneous apoptosis, but not survivin expression, is associated with histomorphologic response to neoadjuvant chemoradiation in rectal cancer. Int J Colorectal Dis 2009;24:1261–1269.CrossRefPubMedGoogle Scholar
  36. 36.
    Miura K, Karasawa H, Sasaki I. cIAP2 as a therapeutic target in colorectal cancer and other malignancies. Expert Opin Ther Targets 2009;13:1333–1345.CrossRefPubMedGoogle Scholar
  37. 37.
    Nakahara T, Takeuchi M, Kinoyama I, Minematsu T, Shirasuna K, Matsuhisa A, et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormonerefractory prostate tumor xenografts. Cancer Res 2007;67:8014–8021.CrossRefPubMedGoogle Scholar
  38. 38.
    Iwasa T, Okamoto I, Suzuki M, Nakahara T, Yamanaka K, Hatashita E, et al. Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines. Clin Cancer Res 2008;14:6496–6504.CrossRefPubMedGoogle Scholar
  39. 39.
    Rödel F, Frey B, Leitmann W, Capalbo G, Weiss C, Rödel C. Survivin antisense oligonucleotides effectively radiosensitize colorectal cancer cells in both tissue culture and murine xenograft models. Int J Radiat Oncol Biol Phys 2008;71:247–255.CrossRefPubMedGoogle Scholar
  40. 40.
    LaCasse EC, Cherton-Horvat GG, Hewitt KE, Jerome LJ, Morris SJ, Kandimalla ER, et al. Preclinical characterization of AEG35156/GEM 640, a second-generation antisense oligonucleotide targeting X-linked inhibitor of apoptosis. Clin Cancer Res 2006;12:5231–5241.CrossRefPubMedGoogle Scholar
  41. 41.
    Silasi DA, Alvero AB, Rutherford TJ, Brown D, Mor G. Phenoxodiol: pharmacology and clinical experience in cancer monotherapy and in combination with chemotherapeutic drugs. Expert Opin Pharmacother 2009;10:1059–1067.CrossRefPubMedGoogle Scholar
  42. 42.
    Saif MW, Tytler E, Lansigan F, Brown DM, Husband AJ. Flavonoids, phenoxodiol, and a novel agent, triphendiol, for the treatment of pancreaticobiliary cancers. Expert Opin Investig Drugs 2009;18:469–479.CrossRefPubMedGoogle Scholar
  43. 43.
    Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature 2000;408:1008–1012.CrossRefPubMedGoogle Scholar
  44. 44.
    Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG. A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 2004;305:1471–1474.CrossRefPubMedGoogle Scholar
  45. 45.
    Sun W, Nikolovska-Coleska Z, Qin D, Sun H, Yang CY, Bai L, et al. Design, synthesis, and evaluation of potent, nonpeptidic mimetics of second mitochondria-derived activator of caspases. J Med Chem 2009;52:593–596.CrossRefPubMedGoogle Scholar
  46. 46.
  47. 47.
    Pajak B, Gajkowska B, Orzechowski A. Sodium butyrate sensitizes human colon adenocarcinoma COLO 205 cells to both intrinsic and TNF-alpha-dependent extrinsic apoptosis. Apoptosis 2009;14:203–217.CrossRefPubMedGoogle Scholar
  48. 48.
    Kim SM, Lee SY, Yuk DY, Moon DC, Choi SS, Kim Y, et al. Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Arch Pharm Res 2009;32:755–765.CrossRefPubMedGoogle Scholar
  49. 49.
    An MJ, Cheon JH, Kim SW, Kim ES, Kim TI, Kim WH. Guggulsterone induces apoptosis in colon cancer cells and inhibits tumor growth in murine colorectal cancer xenografts. Cancer Lett 2009;279:93–100.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Koh Miura
    • 1
  • Wataru Fujibuchi
    • 2
  • Kazuyuki Ishida
    • 3
  • Takeshi Naitoh
    • 1
  • Hitoshi Ogawa
    • 1
  • Toshinori Ando
    • 1
  • Nobuki Yazaki
    • 1
  • Kazuhiro Watanabe
    • 1
  • Sho Haneda
    • 1
  • Chikashi Shibata
    • 1
  • Iwao Sasaki
    • 1
  1. 1.Department of SurgeryTohoku University Graduate School of MedicineSendai, MiyagiJapan
  2. 2.Computational Biology Research CenterNational Institute of Advanced Industrial Science and TechnologyTokyoJapan
  3. 3.Department of PathologyTohoku University HospitalSendaiJapan

Personalised recommendations