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Cilia, adenomatous polyposis coli and associated diseases

Oncogene volume 31, pages 1475–1483 (2012)Cite this article

Abstract

Cilium is a conservative cell organelle, found in many types of cell surfaces. Cilia are tail-like prominence protruding out of the cell surface, capable of locomotion and acting as the cell's signal transduction sensory organs with their complex structures and ingenious function. Studies have shown that ciliary pathological changes and defects are related to the development of many diseases, including renal cysts, infertility, organ reversal, obesity and so on. The inactivation and mutation of cilia-related proteins can cause tumors, such as neoplasms, intestinal cancer, myeloma, rhabdomyosarcoma and adenocarcinoma. Adenomatous polyposis coli (APC) is a kind of multifunctional protein encoded by the APC gene that participates in many vital activities of organisms. The mutation of APC can lead to familial adenomatous polyposis, and also has a role in the development of human tumors, such as gastric cancer, esophageal cancer and breast carcinoma. Recent studies indicate that the abnormal mutation of APC may lead to some diseases caused by abnormal growth of cilia. Herein, the development of studies on cilia, APC and associated diseases are summarized in brief.

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References

  • Afzelius BA . (1985). The immotile-cilia syndrome: a microtubule-associated defect. CRC Crit Rev Biochem 19: 63–87.

    Article  CAS  Google Scholar 

  • Ahmed Y, Hayashi S, Levine A, Wieschaus E . (1998). Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal. Dev Cell 93: 1171–1182.

    CAS  Google Scholar 

  • Angelo AD, Franco B . (2009). The dynamic cilium in human diseases. Pathogenetics 2: 3.

    Article  Google Scholar 

  • Aoki K, Taketo MM . (2007). Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci 120: 3327–3335.

    Article  CAS  Google Scholar 

  • Banizs B, Pike MM, Millican CL, Ferguson WB, Komlosi P, Sheetz J et al. (2005). Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development 132: 5329–5339.

    Article  CAS  Google Scholar 

  • Beroud C, Soussi T . (1996). APC gene: database of germline and somatic mutations in human tumors and cell lines. Nucleic Acids Res 24: 121–124.

    Article  CAS  Google Scholar 

  • Bertario L, Russo A, Sala P, Varesco L, Giarola M, Mondini P et al. (2003). Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis. J Clin Oncol 21: 1698–1707.

    Article  CAS  Google Scholar 

  • Bienz M . (2002). The subcellular destinations of APC proteins. Nat Rev Mol Cell Biol 3: 328–338.

    Article  CAS  Google Scholar 

  • Bisgrove BW, Yost HJ . (2006). The roles of cilia in developmental disorders and disease. Development 133: 4131–4143.

    Article  CAS  Google Scholar 

  • Bnzing T, Simons M, Walz G . (2007). Wnt signalling in polycystic kidney disease. J Am Soc Nephrol 18: 1389–1398.

    Article  Google Scholar 

  • Brault V, Moore R, Kutsch S, Ishibashi M, Rowitch DH, McMahon AP et al. (2001). Inactivation of the β-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128: 1253–1264.

    CAS  Google Scholar 

  • Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Böker T et al. (1995). Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 4: 337–340.

    Article  CAS  Google Scholar 

  • Chodhari R, Mitchison HM, Meeks M . (2004). Cilia, primary ciliary dyskinesia and molecular genetics. Paediatr Respir Rev 5: 69–76.

    Article  CAS  Google Scholar 

  • Cobas M, Wilson A, Ernst B, Mancini SJ, MacDonald HR, Kemler R et al. (2004). β-Catenin is dispensable for hematopoiesis and lymphopoiesis. J Exp Med 199: 221–229.

    Article  CAS  Google Scholar 

  • Davenport JR, Yoder BK . (2005). An incredible decade for the primary cilia: a look at a once-forgotten organelle. Am J Renal Physiol 289: 1159–1169.

    Article  Google Scholar 

  • Debinski HS, Love S, Spigelman AD, Phillips RK . (1996). Colorectal polyp counts and risk in familia adenomatous polyposis. Gastroenterology 110: 1028–1030.

    Article  CAS  Google Scholar 

  • Eley L, Yates LM, Goodship JA . (2005). Cilia and disease. Genet Dis 15: 308–314.

    CAS  Google Scholar 

  • Escudier E, Duquesnoy P, Papon JF, Amselem S . (2009). Ciliary defects and genetics of primary ciliary dyskinesia. Paediatr Respir Rev 10: 51–54.

    Article  Google Scholar 

  • Fearnhead NS, Britton MP, Bodmer WF . (2001). The ABC of APC. Hum Mol Genet 10: 721–733.

    Article  CAS  Google Scholar 

  • Fodde R . (2002). The APC gene in colorectal cancer. Eur J Cancer 38: 867–871.

    Article  CAS  Google Scholar 

  • Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C et al. (2001). Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 3: 433–438.

    Article  CAS  Google Scholar 

  • Freese JL, Pino D, Pleasure SJ . (2010). Wnt signaling in development and disease. Neurobiol Dis 38: 148–153.

    Article  CAS  Google Scholar 

  • Galiatsatos P, Foulkes WD . (2006). Familial adenomatous polyposis. Am J Gastroenterol 101: 385–398.

    Article  Google Scholar 

  • Gerdes JM, Liu Y, Zaghloul NA, Leitch CC, Lawson SS, Kato M et al. (2007). Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nat Genet 39: 1350–1136.

    Article  CAS  Google Scholar 

  • Giardiello FM, Petersen GM, Piantadosi S, Gruber SB, Traboulsi EI, Offerhaus GJ et al. (1997). APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis. Gut 40: 521–525.

    Article  CAS  Google Scholar 

  • Gómez García EB, Knoers NV . (2009). Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder. Lancet Oncol 10: 727–735.

    Article  Google Scholar 

  • Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H et al. (1991). Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66: 589–600.

    Article  CAS  Google Scholar 

  • Hemmer PH, Zeebregts CJ, Van Baarlen J, Klaase JM . (2004). Image of the month. Arch Surg 139: 223.

    Article  Google Scholar 

  • Herrera L, Kakati S, Gibas L, Pietrzak E, Sandbert A . (1986). Brief clinical report: Gardner syndrome in a man with an interstiiial deletion of 5a. Am J Med Genet 25: 473–476.

    Article  CAS  Google Scholar 

  • Hong DH, Pawlyk B, Sokolov M, Strissel KJ, Yang J, Tulloch B et al. (2003). RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia. Invest Ophthalmol Vis Sci 44: 413–2421.

    Article  Google Scholar 

  • Huangfu D, Anderson KV . (2006). Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development 133: 3–14.

    Article  CAS  Google Scholar 

  • Ishidate T, Matsumine A, Toyoshima K, Akiyama T . (2000). The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene 19: 365–372.

    Article  CAS  Google Scholar 

  • Jimbo T, Kawasaki Y, Koyama R, Sato R, Takada S, Haraguchi K et al. (2002). Identifi cation of a link between the tumour suppressor APC and the kinesin superfamily. Nat Cell Biol 4: 323–327.

    Article  CAS  Google Scholar 

  • Joslyn G, Richardson DS, White R, Alber T . (1993). Dimer formation by an N-terminal coiled in the APC protein. Proc Natl Acad Sci USA 90: 11109–11113.

    Article  CAS  Google Scholar 

  • Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Näthke IS . (2001). A role for the adenomatous polyposis coli protein in chromosome segregation. Nat Cell Biol 3: 429–432.

    Article  CAS  Google Scholar 

  • Kawasaki Y, Senda T, Ishidate T, Koyama R, Morishita T, Iwayama Y et al. (2000). Asef, a link between the tumor suppressor APC and G-protein signaling. Science 289: 1194–1197.

    Article  CAS  Google Scholar 

  • Kemler R . (1993). From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet 9: 317–321.

    Article  CAS  Google Scholar 

  • Kinzler KW, Nilbert MC, Su L, Vogelstein B, Bryan TM, Levy DB et al. (1991). Identification of FAP locus genes from chromosome 5q21. Science 253: 661–665.

    Article  CAS  Google Scholar 

  • Klysik M . (2008). Ciliary syndromes and treatment. Pathol Res Pract 204: 77–88.

    Article  CAS  Google Scholar 

  • Kulaga HM, Leitch CC, Eichers ER, Badano JL, Lesemann A, Hoskins BE et al. (2004). Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat Genet 36: 994–998.

    Article  CAS  Google Scholar 

  • Lancaster MA, Gleeson JG . (2009). The primary cilia as a cellular signaling center: lessons from disease. Curr Opin Genet Dev 19: 220–229.

    Article  CAS  Google Scholar 

  • Laurence JZ, Moon RC . (1866). Four cases of retinitis pigmentosa occurring in the same family accompanied by general imperfection of development. Ophthalmol Rev 2: 32–41.

    Google Scholar 

  • Mans DA, Voest EE, Giles RH . (2008). All along the watchtower: is the cilium a tumor suppressor organelle? Biochim Biophys Acta 1786: 114–125.

    CAS  Google Scholar 

  • Matsumine A, Ogai A, Senda T, Okumura N, Satoh K, Baeg GH et al. (1996). Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein. Science 272: 1020–1023.

    Article  CAS  Google Scholar 

  • Michaud EJ, Yoder BK . (2006). The primary cilia in cell signaling and cancer. Cancer Res 6: 6646–6468.

    Google Scholar 

  • Mimori-Kiousue Y, Shiina N, Tsukita S . (2000). Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells. J Cell Biol 48: 505–518.

    Article  Google Scholar 

  • Miyaki M, Yamaguchi T, Iijima T, Takahashi K, Matsumoto H, Yasutome M et al. (2008). Difference in characteristics of APC mutations between colonic and extracolonic tumors of FAP patients: variations with phenotype. Int J Cancer 122: 2491–2497.

    Article  CAS  Google Scholar 

  • Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S et al. (1992). Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet 1: 229–233.

    Article  CAS  Google Scholar 

  • Mykytyn K, Nishimura DY, Searby CC, Beck G, Bugge K, Haines HL et al. (2003). Evaluation of complex inheritance involving the most common Bardet–Biedl syndrome locus (BBS1). Am J Hum Genet 72: 429–437.

    Article  CAS  Google Scholar 

  • Narayan S, Roy D . (2003). Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Mol Cancer 2: 41.

    Article  Google Scholar 

  • Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, Hazucha M et al. (2004). Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med 169: 459–467.

    Article  Google Scholar 

  • Ou G, Blacque OE, Snow JJ, Leroux MR, Scholey JM . (2005). Functional coordination of intraflagellar transport motors. Nature 436: 583–587.

    Article  CAS  Google Scholar 

  • Pan J, Wang Q, Snell WJ . (2005). Cilia-generated signaling and cilia-related disorders. Lab Invest 85: 452–463.

    Article  CAS  Google Scholar 

  • Pisani P, Parkin DM, Bray F, Ferlay J . (1999). Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83: 18–29.

    Article  CAS  Google Scholar 

  • Robert A, Margall-Ducos G, Guidotti JE, Brégerie O, Celati C, Bréchot C et al. (2007). The intraflagellar transport component IFT88/polaris is a centrosomal protein regulating G1-S transition in non-ciliated cells. J Cell Sci 120: 628–637.

    Article  CAS  Google Scholar 

  • Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P . (1996). Binding of GSK3β to the APC-β-catenin complex and regulation of complex assembly. Science 272: 1023–1026.

    Article  CAS  Google Scholar 

  • Rubinfeld B, Albret I, Porfiri E, Munemitsu S, Polakis P . (1997). Loss of beta-catein regulation by the APC tumor suppressor protein correlates with loss of structure due to common somatic mutations of the gene. Cancer Res 57: 4624–4630.

    CAS  Google Scholar 

  • Rubinfeld B, Souza B, Albert I, Müller O, Chamberlain SH, Masiarz FR et al. (1993). Association of the APC gene product with beta-catenin. Science 289: 1194–1197.

    Google Scholar 

  • Saadi-Kheddouci S, Berrebi D, Romagnolo B, Cluzeaud F, Peuchmaur M, Kahn A et al. (2001). Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the β-catenin gene. Oncogene 20: 5972–5981.

    Article  CAS  Google Scholar 

  • Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P et al. (2005). PDGFRa signaling is regulated through the primary cilia in fibroblasts. Curr Biol 15: 1861–1866.

    Article  CAS  Google Scholar 

  • Signoroni S, Frattini M, Negri T, Pastore E, Tamborini E, Casieri P et al. (2007). Cyclooxygenase-2 and platelet-derived growth factor receptors as potential targets in treating aggressive fibromatosis. Clin Cancer Res 13: 5034–5040.

    Article  CAS  Google Scholar 

  • Sloboda RD . (2004). Intraflagellar transport and the flagellar tip complex. J Cell Biochem 94: 266–272.

    Article  Google Scholar 

  • Smits R, Kielman MF, Breukel C, Zurcher C, Neufeld K, Jagmohan-Changur S et al. (1999). Apc1638T: a mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development. Genes Dev 3: 1309–1321.

    Article  Google Scholar 

  • Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordón-Cardo C, Lowe SW et al. (2007). Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11: 9–23.

    Article  CAS  Google Scholar 

  • Tanaka Y, Okada Y, Hirokawa N . (2005). FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435: 172–177.

    Article  CAS  Google Scholar 

  • Thliveris A, Albertsen H, Tuohy T, Carlson M, Groden J, Joslyn G et al. (1996). Long-rang physical map and deletion characterization of the 1100-kb Not I restriction fragment harboring the APC gene. Genomics 34: 268–270.

    Article  CAS  Google Scholar 

  • Tirnauer JS, Bierer BE . (2000). EB1 proteins regulate microtubule dynamics cell polarity and chromosome stability. J Cell Biol 149: 761–766.

    Article  CAS  Google Scholar 

  • Wilson PD . (2004). Polycystic kidney disease. N Engl J Med 350: 151–164.

    Article  CAS  Google Scholar 

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Acknowledgements

This project was supported by grants of National Natural Science Foundation of China (No. 31040018), and the research project was supported by Shanxi scholarship council of China (2010–2012). We wish to thank Dr Enmin Zou of the Department of Biological Sciences of Nicolls State University, USA, for improving the readability of the manuscript.

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  1. The Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Biotechnology, Shanxi University, Taiyuan, China

    Z Li, W Li, L Song & W Zhu

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Li, Z., Li, W., Song, L. et al. Cilia, adenomatous polyposis coli and associated diseases. Oncogene 31, 1475–1483 (2012). https://doi.org/10.1038/onc.2011.351

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