adenomatous polyposis coli protein


Summary: A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.

Top Publications

  1. Buchert M, Athineos D, Abud H, Burke Z, Faux M, Samuel M, et al. Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo. PLoS Genet. 2010;6:e1000816 pubmed publisher
    ..Together, the present genotype-phenotype analysis suggests tissue-specific response levels for the Wnt/beta-catenin pathway that regulate both physiological and pathophysiological conditions. ..
  2. MacFarlane A, Perry C, McEntee M, Lin D, Stover P. Shmt1 heterozygosity impairs folate-dependent thymidylate synthesis capacity and modifies risk of Apc(min)-mediated intestinal cancer risk. Cancer Res. 2011;71:2098-107 pubmed publisher
  3. Quyn A, Appleton P, Carey F, Steele R, Barker N, Clevers H, et al. Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue. Cell Stem Cell. 2010;6:175-81 pubmed publisher
    ..This loss correlates with cell shape changes specifically in the stem cell compartment. Our data suggest that loss of asymmetric division in stem cells might contribute to the oncogenic effect of Apc mutations in gut epithelium. ..
  4. Tran H, Polakis P. Reversible modification of adenomatous polyposis coli (APC) with K63-linked polyubiquitin regulates the assembly and activity of the ?-catenin destruction complex. J Biol Chem. 2012;287:28552-63 pubmed publisher
    ..Together, our results indicate that K63-linked polyubiquitin adducts on APC regulate the assembly and/or efficiency of the ?-catenin destruction complex. ..
  5. Schneikert J, Brauburger K, Behrens J. APC mutations in colorectal tumours from FAP patients are selected for CtBP-mediated oligomerization of truncated APC. Hum Mol Genet. 2011;20:3554-64 pubmed publisher
    ..This suggests that the sensitivity of truncated APC to oligomerization by CtBP constitutes an essential facet of tumour development...
  6. Guillen Ahlers H, Suckow M, Castellino F, Ploplis V. Fas/CD95 deficiency in ApcMin/+ mice increases intestinal tumor burden. PLoS ONE. 2010;5:e9070 pubmed publisher
    ..Fas, a member of the tumor necrosis family, is responsible for initiating the apoptotic pathway when bound to its ligand, Fas-L. Defects in the Fas-mediated apoptotic pathway have been reported in colorectal cancer...
  7. Phelps R, Chidester S, Dehghanizadeh S, Phelps J, Sandoval I, Rai K, et al. A two-step model for colon adenoma initiation and progression caused by APC loss. Cell. 2009;137:623-34 pubmed publisher
    ..Consistent with this model, human FAP adenomas showed robust upregulation of CtBP1 in the absence of detectable nuclear beta-catenin, whereas nuclear beta-catenin was detected in carcinomas. ..
  8. Du Q, Zhang X, Cardinal J, Cao Z, Guo Z, Shao L, et al. Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric oxide synthase expression by inhibiting nuclear factor-kappaB activation in cancer cells. Cancer Res. 2009;69:3764-71 pubmed publisher
    ..These findings underscore the complex role of Wnt/beta-catenin, NF-kappaB, and iNOS signaling in the pathophysiology of inflammation-associated carcinogenesis. ..
  9. Xue B, Dunker A, Uversky V. The roles of intrinsic disorder in orchestrating the Wnt-pathway. J Biomol Struct Dyn. 2012;29:843-61 pubmed
    ..Intrinsically disordered APC helps the collection of ?-catenin from cytoplasm, facilitates the b-catenin delivery to the binding sites on Axin, and controls the final detachment of ?-catenin from Axin. ..

More Information


  1. Chandra S, Wacker I, Appelt U, Behrens J, Schneikert J. A common role for various human truncated adenomatous polyposis coli isoforms in the control of beta-catenin activity and cell proliferation. PLoS ONE. 2012;7:e34479 pubmed publisher
    ..Thus, truncated APC is an essential component of colorectal cancer cells, required for cell proliferation, possibly by adjusting ?-catenin signalling to the "just right" level. ..
  2. Harris E, Nelson W. Adenomatous polyposis coli regulates endothelial cell migration independent of roles in beta-catenin signaling and cell-cell adhesion. Mol Biol Cell. 2010;21:2611-23 pubmed publisher
    ..These results uncouple different APC functions and show that GSK3 beta/CKI phosphorylation regulates APC clusters and cell migration independently of cell-cell adhesion and beta-catenin transcriptional activity. ..
  3. Newton I, Kenneth N, Appleton P, Näthke I, Rocha S. Adenomatous polyposis coli and hypoxia-inducible factor-1{alpha} have an antagonistic connection. Mol Biol Cell. 2010;21:3630-8 pubmed publisher
    ..These results reveal down-regulation of APC as a new mechanism that contributes to the survival advantage induced by hypoxia and also show that loss of APC mutations produces a survival advantage by mimicking hypoxic conditions. ..
  4. Dupasquier S, Abdel Samad R, Glazer R, Bastide P, Jay P, Joubert D, et al. A new mechanism of SOX9 action to regulate PKCalpha expression in the intestine epithelium. J Cell Sci. 2009;122:2191-6 pubmed publisher
    ..These results provide a potential explanation for the decrease of PKCalpha expression in colorectal cancers with constitutive activation of the Wnt-APC pathway. ..
  5. Faux M, Coates J, Kershaw N, Layton M, Burgess A. Independent interactions of phosphorylated ?-catenin with E-cadherin at cell-cell contacts and APC at cell protrusions. PLoS ONE. 2010;5:e14127 pubmed publisher
    ..Localised regulation of APC-phospho-?-catenin complexes may contribute to the tumour suppressor activity of APC...
  6. Gay L, Mitrou P, Keen J, Bowman R, Naguib A, Cooke J, et al. Dietary, lifestyle and clinicopathological factors associated with APC mutations and promoter methylation in colorectal cancers from the EPIC-Norfolk study. J Pathol. 2012;228:405-15 pubmed publisher
    ..75). In conclusion, APC(+) and PM(+) CRCs may be influenced by diet and GC-to-AT mutations in APC are associated with processed meat consumption, suggesting a mechanistic link with dietary alkylating agents, such as N-nitroso compounds. ..
  7. Zhang Z, Lin K, Gao L, Chen L, Shi X, Wu G. Crystal structure of the armadillo repeat domain of adenomatous polyposis coli which reveals its inherent flexibility. Biochem Biophys Res Commun. 2011;412:732-6 pubmed publisher
    ..We propose that this intrinsic flexibility might be an inherent property of ARM domains in general. ..
  8. Chaw S, Abdul Majeed A, Dalley A, Chan A, Stein S, Farah C. Epithelial to mesenchymal transition (EMT) biomarkers--E-cadherin, beta-catenin, APC and Vimentin--in oral squamous cell carcinogenesis and transformation. Oral Oncol. 2012;48:997-1006 pubmed publisher
    ..Aberrant expression of β-catenin, APC and Vimentin are potential markers of malignant transformation. ..
  9. Li A, Xing Y, Chan B, Heisterkamp N, Groffen J, Borok Z, et al. Cell type-specific expression of adenomatous polyposis coli in lung development, injury, and repair. Dev Dyn. 2010;239:2288-97 pubmed publisher
    ..nonprogenitor cells suggests a functional role in cell-type specification. Subcellular localization changes of Apc in response to naphthalene injury suggest a role in cell shape and cell migration. ..
  10. Lang J, Maeda Y, Bannerman P, Xu J, Horiuchi M, Pleasure D, et al. Adenomatous polyposis coli regulates oligodendroglial development. J Neurosci. 2013;33:3113-30 pubmed publisher
    ..Together, our data support the hypothesis that APC regulates oligodendrocyte differentiation through both ?-catenin-dependent and additional ?-catenin-independent mechanisms. ..
  11. KENNELL J, Cadigan K. APC and beta-catenin degradation. Adv Exp Med Biol. 2009;656:1-12 pubmed
  12. Xu H, Posner G, Stevenson M, Campbell F. Apc(MIN) modulation of vitamin D secosteroid growth control. Carcinogenesis. 2010;31:1434-41 pubmed publisher
    ..APC heterozygosity may promote favourable tissue- or tumour-specific conditions for growth control by vitamin D secosteroid treatment. ..
  13. Pecina Slaus N, Majić Z, Musani V, Zeljko M, Cupic H. Report on mutation in exon 15 of the APC gene in a case of brain metastasis. J Neurooncol. 2010;97:143-8 pubmed publisher
    ..In our opinion, such silent mutations should also be incorporated in mutation detection rate and validation. ..
  14. Bhandaru M, Kempe D, Rotte A, Rexhepaj R, Kuhl D, Lang F. Hyperaldosteronism, hypervolemia, and increased blood pressure in mice expressing defective APC. Am J Physiol Regul Integr Comp Physiol. 2009;297:R571-5 pubmed publisher
    ..The experiments reveal an influence of defective APC on adrenal hormone release and renal function, effects partially but not completely explained by APC dependence of SGK1 expression. ..
  15. Etienne Manneville S. APC in cell migration. Adv Exp Med Biol. 2009;656:30-40 pubmed
  16. Li V, Ng S, Boersema P, Low T, Karthaus W, Gerlach J, et al. Wnt signaling through inhibition of ?-catenin degradation in an intact Axin1 complex. Cell. 2012;149:1245-56 pubmed publisher
    ..Subsequently, newly synthesized ?-catenin can accumulate in a free cytosolic form and engage nuclear TCF transcription factors. ..
  17. Voorham Q, Carvalho B, Spiertz A, van Grieken N, Mongera S, Rondagh E, et al. Chromosome 5q loss in colorectal flat adenomas. Clin Cancer Res. 2012;18:4560-9 pubmed
    ..Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, that is, chromosomal instability, between flat and polypoid colorectal adenomas...
  18. Morishita E, Murayama K, Kato Murayama M, Ishizuka Katsura Y, Tomabechi Y, Hayashi T, et al. Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68. Structure. 2011;19:1496-508 pubmed publisher
    ..Structural comparisons revealed different modes of ligand recognition between the Arm domains of APC and other Arm-containing proteins. ..
  19. Kohler E, Brauburger K, Behrens J, Schneikert J. Contribution of the 15 amino acid repeats of truncated APC to beta-catenin degradation and selection of APC mutations in colorectal tumours from FAP patients. Oncogene. 2010;29:1663-71 pubmed publisher
    ..The analysis of the distribution of truncating mutations along the APC sequence in colorectal tumours from FAP patients revealed that the first 15R is one target of the positive selection of mutations that lead to tumour development...
  20. Zhang Z, Li H, Chen L, Lu X, Zhang J, Xu P, et al. Molecular basis for the recognition of adenomatous polyposis coli by the Discs Large 1 protein. PLoS ONE. 2011;6:e23507 pubmed publisher
    ..The results provide new insights into the binding mode of a defined C-terminal segment of APC by the PDZ domains of DLG1. ..
  21. Andresen P, Heimdal K, Aaberg K, Eklo K, Eklo K, Ariansen S, et al. APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations. J Cancer Res Clin Oncol. 2009;135:1463-70 pubmed publisher
    ..A high ratio of novel APC mutations continues to contribute to APC mutation heterogeneity causing FAP. This is the first comprehensive report of APC germline mutation spectrum in Norway. ..
  22. Zhang J, Neisa R, Mao Y. Oncogenic Adenomatous polyposis coli mutants impair the mitotic checkpoint through direct interaction with Mad2. Mol Biol Cell. 2009;20:2381-8 pubmed publisher
    ..Expressing a tumor-associated N-APC mutant in mammalian cells with an intact mitotic checkpoint produces premature anaphase onset with missegregated chromosomes. ..
  23. Zhang Z, Chen L, Gao L, Lin K, Zhu L, Lu Y, et al. Structural basis for the recognition of Asef by adenomatous polyposis coli. Cell Res. 2012;22:372-86 pubmed publisher
    ..Our structures thus elucidate the molecular mechanism of Asef recognition by APC, as well as provide a potential target for pharmaceutical intervention against cancers. ..
  24. Larabee J, Shakir S, Hightower L, Ballard J. Adenomatous polyposis coli protein associates with C/EBP beta and increases Bacillus anthracis edema toxin-stimulated gene expression in macrophages. J Biol Chem. 2011;286:19364-72 pubmed publisher
    ..These results indicate that ET stimulates gene expression by promoting the formation of an inducible protein complex consisting of APC and C/EBP ?. ..
  25. Rohlin A, Engwall Y, Fritzell K, Göransson K, Bergsten A, Einbeigi Z, et al. Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis. Oncogene. 2011;30:4977-89 pubmed publisher
  26. Tanwar P, Zhang L, TEIXEIRA J. Adenomatous polyposis coli (APC) is essential for maintaining the integrity of the seminiferous epithelium. Mol Endocrinol. 2011;25:1725-39 pubmed publisher
  27. Benchabane H, Ahmed Y. The adenomatous polyposis coli tumor suppressor and Wnt signaling in the regulation of apoptosis. Adv Exp Med Biol. 2009;656:75-84 pubmed
    ..This chapter summarizes our current understanding of the role of APC and Wnt signaling in the regulation of apoptosis, based upon studies from fly and mouse in vivo models, as well as cultured carcinoma cells. ..
  28. Restucci B, Martano M, De Vico G, Lo Muzio L, Maiolino P. Expression of E-cadherin, beta-catenin and APC protein in canine colorectal tumours. Anticancer Res. 2009;29:2919-25 pubmed
  29. Hilger M, Mann M. Triple SILAC to determine stimulus specific interactions in the Wnt pathway. J Proteome Res. 2012;11:982-94 pubmed publisher
    ..The core destruction complex itself, which regulates beta-catenin stability as the key step in canonical Wnt signaling, remained essentially unchanged. ..
  30. Crist R, Roth J, Baran A, McEntee B, Siracusa L, Buchberg A. The armadillo repeat domain of Apc suppresses intestinal tumorigenesis. Mamm Genome. 2010;21:450-7 pubmed publisher
    ..These data suggest that the armadillo repeat domain of the Apc protein suppresses tumor initiation in the murine intestine while also promoting tumor growth. ..
  31. Shintani T, Takeuchi Y, Fujikawa A, Noda M. Directional neuronal migration is impaired in mice lacking adenomatous polyposis coli 2. J Neurosci. 2012;32:6468-84 pubmed publisher
    ..Thus, APC2 is an essential mediator of the cytoskeletal regulation at leading edges in response to extracellular signals. ..
  32. Liu L, Kron K, Pethe V, Demetrashvili N, Nesbitt M, Trachtenberg J, et al. Association of tissue promoter methylation levels of APC, TGF?2, HOXD3 and RASSF1A with prostate cancer progression. Int J Cancer. 2011;129:2454-62 pubmed publisher
    ..017). Our study demonstrated that quantitative increase in promoter methylation levels of APC, HOXD3 and TGF?2 are associated with PCa progression. ..
  33. Filipe B, Baltazar C, Albuquerque C, Fragoso S, Lage P, Vitoriano I, et al. APC or MUTYH mutations account for the majority of clinically well-characterized families with FAP and AFAP phenotype and patients with more than 30 adenomas. Clin Genet. 2009;76:242-55 pubmed publisher
    ..The phenotypes of the mutation-negative patients suggest distinct etiologies in these cases...
  34. Huang S, Ting W, Chen L, Huang L, Liu C, Chen C, et al. Association analysis of Wnt pathway genes on prostate-specific antigen recurrence after radical prostatectomy. Ann Surg Oncol. 2010;17:312-22 pubmed publisher
    ..037) compared with the GG genotype. This is the first report documenting the potential prognostic role of the APC rs3846716 GA/AA genotype on PSA recurrence after RP. ..
  35. Luo F, Brooks D, Ye H, Hamoudi R, Poulogiannis G, Patek C, et al. Mutated K-ras(Asp12) promotes tumourigenesis in Apc(Min) mice more in the large than the small intestines, with synergistic effects between K-ras and Wnt pathways. Int J Exp Pathol. 2009;90:558-74 pubmed publisher
  36. Prosperi J, Becher K, Willson T, Collins M, Witte D, Goss K. The APC tumor suppressor is required for epithelial integrity in the mouse mammary gland. J Cell Physiol. 2009;220:319-31 pubmed publisher
    ..These results suggest that APC expression is tightly regulated during mammary gland development and is required for normal mammary homeostasis and tumor suppression primarily through maintaining epithelial integrity. ..
  37. Voorham Q, Rondagh E, Knol D, van Engeland M, Carvalho B, Meijer G, et al. Tracking the molecular features of nonpolypoid colorectal neoplasms: a systematic review and meta-analysis. Am J Gastroenterol. 2013;108:1042-56 pubmed publisher
    ..Prospective, multicenter studies are needed to clarify the molecular pathways underlying nonpolypoid colorectal carcinogenesis and potential implications for surveillance intervals. ..
  38. Schneikert J, Vijaya Chandra S, Ruppert J, Ray S, Wenzel E, Behrens J. Functional comparison of human adenomatous polyposis coli (APC) and APC-like in targeting beta-catenin for degradation. PLoS ONE. 2013;8:e68072 pubmed publisher
  39. Miclea R, Karperien M, Langers A, Robanus Maandag E, van Lierop A, van der Hiel B, et al. APC mutations are associated with increased bone mineral density in patients with familial adenomatous polyposis. J Bone Miner Res. 2010;25:2624-32 pubmed publisher
    ..Our data suggest a state of "controlled" activation of the Wnt signaling pathway in heterozygous carriers of APC mutations, most likely owing to upregulation of cytoplasmic ?-catenin levels. ..
  40. Voorham Q, Carvalho B, Spiertz A, Claes B, Mongera S, van Grieken N, et al. Comprehensive mutation analysis in colorectal flat adenomas. PLoS ONE. 2012;7:e41963 pubmed publisher
  41. Minde D, Anvarian Z, Rüdiger S, Maurice M. Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?. Mol Cancer. 2011;10:101 pubmed publisher
    ..Insight in the underlying molecular events will be invaluable in the development of novel strategies to counter dysregulated Wnt signaling by APC mutations in cancer...
  42. Brocardo M, Borowiec J, Henderson B. Adenomatous polyposis coli protein regulates the cellular response to DNA replication stress. Int J Biochem Cell Biol. 2011;43:1354-64 pubmed publisher
  43. Gaujoux S, Pinson S, Gimenez Roqueplo A, Amar L, Ragazzon B, Launay P, et al. Inactivation of the APC gene is constant in adrenocortical tumors from patients with familial adenomatous polyposis but not frequent in sporadic adrenocortical cancers. Clin Cancer Res. 2010;16:5133-41 pubmed publisher
    ..Both APC and WTX are involved in Wnt/?-catenin pathway regulation and may play a role in ACT tumorigenesis. The aim of this study was to report if APC and WTX may be associated with FAP-associated and sporadic ACT...
  44. Lagarde A, Rouleau E, Ferrari A, Noguchi T, Qiu J, Briaux A, et al. Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP. J Med Genet. 2010;47:721-2 pubmed publisher
    ..The work presented here delineates precisely the APC mutation spectrum from 15 years of systematic molecular screening which identified 863 independent alterations in the French population...
  45. Caldwell C, Kaplan K. The role of APC in mitosis and in chromosome instability. Adv Exp Med Biol. 2009;656:51-64 pubmed
    ..In this chapter, we will review the literature linking APC to regulation of mitotic fidelity and discuss the implications for dividing epithelial cells in the intestine. ..
  46. Neufeld K. Nuclear APC. Adv Exp Med Biol. 2009;656:13-29 pubmed
    ..Clear definition of APC's nuclear function(s) will expand the possibilities for early colorectal cancer diagnostics and therapeutics targeted to APC. ..
  47. Gaspar C, Franken P, Molenaar L, Breukel C, van der Valk M, Smits R, et al. A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis. PLoS Genet. 2009;5:e1000547 pubmed publisher
    ..The striking phenotype of Apc(+/1572T) mice suggests that specific dosages of Wnt/beta-catenin signaling activity differentially affect tissue homeostasis and initiate tumorigenesis in an organ-specific fashion. ..
  48. Hosoya K, Yamashita S, Ando T, Nakajima T, Itoh F, Ushijima T. Adenomatous polyposis coli 1A is likely to be methylated as a passenger in human gastric carcinogenesis. Cancer Lett. 2009;285:182-9 pubmed publisher
    ..These findings strongly indicated that methylation of APC promoter 1A is a passenger, and suggested that marked down-regulation of 1B expression could be related to formation of a field predisposed to gastric cancers. ..
  49. Okada K, Bartolini F, Deaconescu A, Moseley J, Dogic Z, Grigorieff N, et al. Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1. J Cell Biol. 2010;189:1087-96 pubmed publisher
    ..These observations define a new function for APC and support an emerging view of collaboration between distinct actin assembly-promoting factors with complementary activities. ..
  50. Kwong L, Dove W. APC and its modifiers in colon cancer. Adv Exp Med Biol. 2009;656:85-106 pubmed
  51. Barker N, Ridgway R, van Es J, van de Wetering M, Begthel H, van den Born M, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457:608-11 pubmed publisher
    ..Even after 30weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia...
  52. Collin L, Schlessinger K, Hall A. APC nuclear membrane association and microtubule polarity. Biol Cell. 2008;100:243-52 pubmed
    ..We find that APC, through a direct interaction with the NPC (nuclear pore complex) protein Nup153 (nucleoporin 153), promotes the association of microtubules with the nuclear membrane. ..
  53. Kroboth K, Newton I, Kita K, Dikovskaya D, Zumbrunn J, Waterman Storer C, et al. Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability. Mol Biol Cell. 2007;18:910-8 pubmed
    ..These data demonstrate that cell migration and microtubule stability are linked to APC status, thereby revealing a weakness in APC-deficient cells with potential therapeutic implications. ..
  54. Aguilera O, Fraga M, Ballestar E, Paz M, Herranz M, Espada J, et al. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. Oncogene. 2006;25:4116-21 pubmed
  55. Mili S, Moissoglu K, Macara I. Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions. Nature. 2008;453:115-9 pubmed publisher
    ..APC is required for the accumulation of transcripts in protrusions. Our results suggest a new type of RNA anchoring mechanism as well as a new, unanticipated function for APC in localizing RNAs. ..
  56. Hebbar S, Guillotte A, Mesngon M, Zhou Q, Wynshaw Boris A, Smith D. Genetic enhancement of the Lis1+/- phenotype by a heterozygous mutation in the adenomatous polyposis coli gene. Dev Neurosci. 2008;30:157-70 pubmed
    ..Together, our findings point to a previously unknown interaction between APC and Lis1 during mammalian brain development. ..