The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
The APC tumour suppressor has a nuclear export function
Abstract
The adenomatous polpyposis coli (APC) protein is mutated in most colorectal tumours. Nearly all APC mutations are truncations, and many of these terminate in the mutation cluster region located halfway through the protein. In cancer cells expressing mutant APC, beta-catenin is stabilized and translocates into the nucleus to act as a transcriptional co-activator of T-cell factor. During normal development, APC also promotes the destabilization of beta-catenin and Drosophila Armadillo. It does so by binding to the Axin complex which earmarks beta-catenin/Armadillo for degradation by the proteasome pathway. APC has a regulatory role in this process, which is poorly understood. Here we show that APC contains highly conserved nuclear export signals 3' adjacent to the mutation cluster region that enable it to exit from the nucleus. This ability is lost in APC mutant cancer cells, and we provide evidence that beta-catenin accumulates in the nucleus as a result. Thus, the ability of APC to exit from the nucleus appears to be critical for its tumour suppressor function.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As mentioned above, asymmetric membrane accumulation of Dsh is important for the non-canonical pathway and convergent extension movements.118–120”
From Wnt signal transduction pathways (2008) · cites this paper as [119]
Citations
Cites
Lessons from hereditary colorectal cancer
Kinzler, K. W., & Vogelstein, B. (1996) · Cell · doi:10.1016/s0092-8674(00)81333-1 · Cited by 4,919
Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Morin, P. J., Sparks, A. B., Kořínek, V., Barker, N., Clevers, H. C., Vogelstein, B., & Kinzler, K. W. (1997) · Science · doi:10.1126/science.275.5307.1787 · Cited by 4,000
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma
Korinek, V., Barker, N., Morin, P. J., van Wichen, D., de Weger, R., Kinzler, K. W., Vogelstein, B., & Clevers, H. (1997) · Science · doi:10.1126/science.275.5307.1784 · Cited by 2,905
CRM1 Is an Export Receptor for Leucine-Rich Nuclear Export Signals
Fornerod, M. W. J., Ohno, M., Yoshida, M., & Mattaj, I. W. (1997) · Cell · doi:10.1016/s0092-8674(00)80371-2 · Cited by 2,086
Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3β
Behrens, J., Jerchow, B., Würtele, M., Grimm, J., Asbrand, C., Wirtz, R. M., Kühl, M., Wedlich, D., & Birchmeier, W. (1998) · Science · doi:10.1126/science.280.5363.596 · Cited by 1,255
Wnt Signaling in Oncogenesis and Embryogenesis--a Look Outside the Nucleus
Peifer, M., & Polakis, P. (2000) · Science · doi:10.1126/science.287.5458.1606 · Cited by 1,253
CRM1 is responsible for intracellular transport mediated by the nuclear export signal
Fukuda, M., Asano, S., Nakamura, T., Adachi, M., Yoshida, M., Yanagida, M., & Nishida, E. (1997) · Nature · doi:10.1038/36894 · Cited by 1,213
Association of the APC Tumor Suppressor Protein with Catenins
Su, L.-K., Vogelstein, B., & Kinzler, K. W. (1993) · Science · doi:10.1126/science.8259519 · Cited by 1,193
Munemitsu, S. M., Albert, I., Souza, B., Rubinfeld, B., & Polakis, P. G. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.3046 · Cited by 1,021
Hart, M. J., Santos, R. D. L., Albert, I., Rubinfeld, B., & Polakis, P. G. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70226-x · Cited by 850
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–343 of 343
Expressions of two adenomatous polyposis coli and E-cadherin proteins on human colorectal cancers
Furuta, K., Yoshioka, S., Okabe, S., Ikeda, M., Oginosawa, M., Ikeda, S., Nakayama, Y., Kikuchi, M., & Hamilton, S. R. (2003) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-002-0757-z · Cited by 3
“In their article, they introduced the concept that APC contains nuclear export signals (NES) [8, 18] and, further, some of the mutant and truncated APC retained only the N-terminal NES.”
BackgroundAACR special meeting in cancer research: colon cancer--genetics to prevention.
Johnstone, C. N., Chang, L. M., & Ernst, M. (2002) · PubMed · Cited by 3
Biology and Molecular Genetics of Colorectal Cancer
Kuwada, S. K., Neklason, D. W., & Burt, R. W. (2002) · Humana Press eBooks · doi:10.1007/978-1-59259-160-2_1 · Cited by 2
Phytochemical remedies: a key strategy towards reversing the aggressive murine colon cancer
Attia, N. A., Sayed, A. H., Mahmoud, N. S., & Ahmed, H. H. (2017) · Medicinal Chemistry Research · doi:10.1007/s00044-017-1960-4 · Cited by 2
“the nucleus and targeting it for degradation in the cytoplasm (Rosin-Arbesfeld et al. 2000; Khalilzadeha et al. 2016).”
Novel p53-Based Therapies: Strategies and Future Prospects
Laı́n, S., & Lane, D. P. (2005) · Springer eBooks · doi:10.1007/978-1-4020-2922-6_16 · Cited by 2
Developmental Signaling Networks
Bommer, G. T., & Fearon, E. R. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-382026-6.00009-9 · Cited by 2
Effect of Aspirin on Nuclear β-Catenin Expression in Sporadic Colorectal Adenomas
Kim, H. J., Lee, S. J., Park, S. C., Choi, D. H., Kang, C. D., & Kang, G. (2013) · Intestinal Research · doi:10.5217/ir.2013.11.4.283 · Cited by 1
Wnt Signal Transduction and Its Involvement in Human Diseases
Jho, E. (2005) · Journal of Korean Endocrine Society · doi:10.3803/jkes.2005.20.4.306 · Cited by 1
“핵 내로 들어간 β-catenin은 transcription을 활성화시킨 후, Wnt signaling 존재 하에 level이 증가되고 핵 내로 같 이 들어오는 APC에 의해서 cytoplasm으로 export된다고 제 안되었다[48,49].”
Structure of the Amino‐Terminal Nuclear Export Domain of the APC Tumor Suppressor Protein
Tickenbrock, L., Cramer, J., Vetter, I. R., & MÜLLER, O. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04616.x · Cited by 1
A gust of WNT: analysis of the canonical WNT pathway.
Giunta, S. (2009) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 1
Liu, C., Régimbald‐Dumas, Y., Zhang, X., & He, X. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-394447-4.30008-6 · Cited by 1
HNF4α is a target of the Wnt/β-catenin pathway and regulates colorectal carcinogenesisPreprint
Sang, L., Bai, W., Lu, C., Dong, R., Hao, Q., Zhang, Y., Sun, R., Shen, J., Sun, Y., & Sun, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.25.586542 · Cited by 1
Perfil mutacional do gene APC em pacientes com polipose adenomatosa familial no estado do Pará
Cavalléro, S. R. D. A. (2014) · Americanae (AECID Library)
Tumor Suppressor APC and Musashi1: Double-Negative Feedback, Wnt Signaling and Colon Cancer
Spears, E. (2011) · KU ScholarWorks (University of Kansas)
Prostate Cancer Progression to Androgen Independent Disease: The Role of the Wnt/β-Catenin Pathway
Jacqueline, R., Huang, Y., & Pers, S. (2011) · InTech eBooks · doi:10.5772/26201
“Firstly, as a nuclear exporter of ┚-catenin, it is able to restrict TCF interaction and thus gene transcription (Henderson, 2000; Rosin-arbesfeld et al., 2000; van de Wetering et al., 1997; Xing et al., 2004) This model can be partly supported by the nuclear accumulation of ┚-catenin in colorectal cancer cells (SW480)…”
BackgroundIKK and Beta-Catenin in Breast Cancer
Teo, M. (2002) · Defense Technical Information Center (DTIC) · doi:10.21236/ada407807
Oncogenic β-catenin signaling networks in colorectal cancer
Fuchs, S. Y., Ougolkov, A. V., Spiegelman, V. S., & Minamoto, T. (2006) · Institutional Repositories DataBase (IRDB)
Qazi, F., Khan, T., Naqshi, H. R., Rasool, S., Chowdri, N. A., & Ganai, B. A. (2014) · International Journal of Sciences: Basic and Applied Research
Dietary modulation of β-catenin signalling in an experimental model of colon cancer
Misikangas, M. (2007) · Työväentutkimus Vuosikirja
Applying toponome imaging system for studying colon cancer
Bhattacharya, S. (2026) · Warwick Research Archive Portal (University of Warwick) · doi:10.82444/warw.33667612
Convergence analysis of clonal selection algorithm based on BCA
Fang, X., Xue-hai, M. U., Ling-bing, L. I. U., & Wang, X. (2010) · Journal of Computer Applications · doi:10.3724/sp.j.1087.2010.00772
Molecular Pathology and Diagnostics of Colorectal Cancer
Shackelford, R. E., Nasir, A., Hakam, A., Shibata, D., Yeatman, T. J., & Coppola, D. (2013) · Springer eBooks · doi:10.1007/978-94-007-7192-5_5
Cadheri nan dCateni nAlteration si nHuma nCancer
Warticle, R. (2002)
Nuclear β-Catenin Signaling as a Target for Anticancer Drug Development
Chung, E. J., Bonvini, P., Oh, H. J., Neckers, L., & Trepel, J. B. (2002) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-1-59259-153-4_5
Towards functional multiscale analysis of colorectal cancer
Briffa, R. (2014) · ERA
Role of eEF1A in the Nuclear Export of the VHL Tumour Suppressor Protein
Francisco, C. B. (2012) · uO Research (University of Ottawa) · doi:10.20381/ruor-6012
“A mutated form of the adenomatous polypsis coli (APC) tumour suppressor protein results in its inability to export into the cytoplasm, where it plays critical roles in reducing the transcriptional ability of β-catenin (Davis et al., 2007; Rosin-Arbesfeld et al., 2000).”
BackgroundThe expression and function of secreted frizzled-related protein 4 in human serous ovarian carcinoma
Drake, J. (2006) · UWA Profiles and Research Repository (University of Western Australia)
Satler, J. D., Carstens, B. C., & Hedin, M. C. (2015) · DRYAD · doi:10.5061/dryad.68s40.2/3.2
Ha, J. R. (2012) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3zk55v6g
Fuerer, C. (2004) · reroDoc Digital Library · doi:10.22005/bcu.15988
Developmental Signaling Networks Wnt/β-Catenin Signaling in the Gastrointestinal Tract
Bommer, G. T., & Fearon, E. R. (2006) · Elsevier eBooks · doi:10.1016/b978-012088394-3/50011-8
β-Catenin, its Binding Partners and Signalling Mechanisms: Implications in Prostate Cancer
Davies, G., Harrison, G. M., & Mason, M. D. (2007) · Springer eBooks · doi:10.1007/978-1-4020-5847-9_9
Green, K. J. (2001) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1001734.8358
Narayan, S. (2007) · Humana Press eBooks · doi:10.1007/978-1-59259-963-9_73
WARDLE, E. N. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-538-5_18
Roy, F. M. V. (2008) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1122828.579916
BCAS2 promotes primitive hematopoiesis by sequestering β-catenin within the nucleus
Ning, G., Lin, Y., Ma, H., Zhang, J., Yang, L., Liu, Z., Li, L., He, X., & Wang, Q. (2025) · eLife · doi:10.7554/elife.100497.3
BCAS2 promotes primitive hematopoiesis by sequestering β-catenin within the nucleusPreprint
Ning, G., Lin, Y., Ma, H., Zhang, J., Yang, L., Liu, Z., Li, L., He, X., & Wang, Q. (2024) · eLife · doi:10.7554/elife.100497.1
Wnt/β-catenin/HNF4α feedback loop facilitates colorectal tumorigenesis and malignancyPreprint
Bai, W., Sang, L., Lu, C., Dong, R., Hao, Q., Zhang, Y., Sun, R., Shen, J., Zhu, W., Sun, Y., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6208041/v1
Generation and analysis of mouse models of aberrant β-catenin function
Cuadrado, P. M. R. (2011) · UCL Discovery (University College London)
Flacelière, M. (2012) · theses.fr (ABES) · doi:10.70675/279c25e4z8fb5z462fz888bz9bae48f71e26
WNT/β-catenin signaling: implications for homeostasis and tumorigenesis in the esophagus
Chen, Z., Guo, X., Peppelenbosch, M. P., & Fuhler, G. M. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189722
APC-dependent regulation of polyamine metabolism and apoptosis in human colon tumor cells
Fultz, K. E. (2002) · UA Campus Repository (The University of Arizona)
Metadata
- Authors
- Rosin-Arbesfeld, R., Townsley, F., & Bienz, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Bienz, Mariann
- ORCID
- Bienz, Mariann
- Venue
- Nature
- Published
- 2000-08
- Volume
- 406
- Issue
- 6799
- Pages
- 1009-1012
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1666932156
- Cited by
- 343
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 12 · 2012: 10
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- nuclear export, nuclear export signal, β-catenin stabilization, colorectal cancer, proteasomal degradation, armadillos, mutation cluster region, tumor suppressor function
- MeSH terms
- Amino Acid Sequence, Animals, Biological Transport, Cell Nucleus, Cytoskeletal Proteins, Drosophila, Fatty Acids, Unsaturated, Multigene Family, Genetic Complementation Test, Humans, Molecular Sequence Data, Mutation, Peptide Fragments, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Colorectal Neoplasms, Trans-Activators, Conserved Sequence, Genes, Reporter, COS Cells, Adenomatous Polyposis Coli Protein, beta Catenin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
