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Science 21 March 1997:
Vol. 275. no. 5307, pp. 1787 - 1790
DOI: 10.1126/science.275.5307.1787
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Reports

Activation of beta -Catenin-Tcf Signaling in Colon Cancer by Mutations in beta -Catenin or APC

Patrice J. Morin, * Andrew B. Sparks, * Vladimir Korinek, Nick Barker, Hans Clevers, Bert Vogelstein, Kenneth W. Kinzler †

Inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene initiates colorectal neoplasia. One of the biochemical activities associated with the APC protein is down-regulation of transcriptional activation mediated by beta -catenin and T cell transcription factor 4 (Tcf-4). The protein products of mutant APC genes present in colorectal tumors were found to be defective in this activity. Furthermore, colorectal tumors with intact APC genes were found to contain activating mutations of beta -catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of beta -catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or beta -catenin.

P. J. Morin and B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
A. B. Sparks and K. W. Kinzler, Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
V. Korinek, N. Barker, H. Clevers, Department of Immunology, University Hospital, 35008 GA, Utrecht, The Netherlands.
*   These authors contributed equally to this work.

†   To whom correspondence should be addressed.

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   Abstract »    Full Text »    PDF »
Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium.
P. Bastide, C. Darido, J. Pannequin, R. Kist, S. Robine, C. Marty-Double, F. Bibeau, G. Scherer, D. Joubert, F. Hollande, et al. (2007)
J. Cell Biol. 178, 635-648
   Abstract »    Full Text »    PDF »
Haploinsufficiency of Kruppel-Like Factor 4 Promotes Adenomatous Polyposis Coli Dependent Intestinal Tumorigenesis.
A. M. Ghaleb, B. B. McConnell, M. O. Nandan, J. P. Katz, K. H. Kaestner, and V. W. Yang (2007)
Cancer Res. 67, 7147-7154
   Abstract »    Full Text »    PDF »
Transcriptional network governing the angiogenic switch in human pancreatic cancer.
A. Abdollahi, C. Schwager, J. Kleeff, I. Esposito, S. Domhan, P. Peschke, K. Hauser, P. Hahnfeldt, L. Hlatky, J. Debus, et al. (2007)
PNAS 104, 12890-12895
   Abstract »    Full Text »    PDF »
WNTs in the Ovine Uterus: Potential Regulation of Periimplantation Ovine Conceptus Development.
K. Hayashi, R. C. Burghardt, F. W. Bazer, and T. E. Spencer (2007)
Endocrinology 148, 3496-3506
   Abstract »    Full Text »    PDF »
Docosahexaenoic acid induces proteasome-dependent degradation of {beta}-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2.
G. Calviello, F. Resci, S. Serini, E. Piccioni, A. Toesca, A. Boninsegna, G. Monego, F. O. Ranelletti, and P. Palozza (2007)
Carcinogenesis 28, 1202-1209
   Abstract »    Full Text »    PDF »
Lysophosphatidic Acid Facilitates Proliferation of Colon Cancer Cells via Induction of Kruppel-like Factor 5.
H. Zhang, A. Bialkowska, R. Rusovici, S. Chanchevalap, H. Shim, J. P. Katz, V. W. Yang, and C. C. Yun (2007)
J. Biol. Chem. 282, 15541-15549
   Abstract »    Full Text »    PDF »
Axin Inhibits Extracellular Signal-regulated Kinase Pathway by Ras Degradation via beta-Catenin.
S. H. Jeon, J.-Y. Yoon, Y.-N. Park, W.-J. Jeong, S. Kim, E.-H. Jho, Y.-J. Surh, and K.-Y. Choi (2007)
J. Biol. Chem. 282, 14482-14492
   Abstract »    Full Text »    PDF »
Subcellular Localization of the Spindle Proteins Aurora A, Mad2, and BUBR1 Assessed by Immunohistochemistry.
E. Burum-Auensen, P. M. De Angelis, A. R. Schjolberg, K. L. Kravik, M. Aure, and O. P. F. Clausen (2007)
J. Histochem. Cytochem. 55, 477-486
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Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the {beta}-Catenin/Tcf Signaling Pathway.
H. Tomita, Y. Yamada, T. Oyama, K. Hata, Y. Hirose, A. Hara, T. Kunisada, Y. Sugiyama, Y. Adachi, H. Linhart, et al. (2007)
Cancer Res. 67, 4079-4087
   Abstract »    Full Text »    PDF »
Induction of inducible nitric oxide synthase: a protective mechanism in colitis-induced adenocarcinoma.
R. Zhang, A. Ma, S. J. Urbanski, and D.-M. McCafferty (2007)
Carcinogenesis 28, 1122-1130
   Abstract »    Full Text »    PDF »
Absence of Stabilizing Mutations of {beta}-Catenin Encoded by CTNNB1 Exon 3 in a Large Series of Sporadic Parathyroid Adenomas.
J. Costa-Guda and A. Arnold (2007)
J. Clin. Endocrinol. Metab. 92, 1564-1566
   Abstract »    Full Text »    PDF »
Long-term feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling in rats.
T. Fujise, R. Iwakiri, T. Kakimoto, R. Shiraishi, Y. Sakata, B. Wu, S. Tsunada, A. Ootani, and K. Fujimoto (2007)
Am J Physiol Gastrointest Liver Physiol 292, G1150-G1156
   Abstract »    Full Text »    PDF »
Activation of Tumor-Specific Splice Variant Rac1b by Dishevelled Promotes Canonical Wnt Signaling and Decreased Adhesion of Colorectal Cancer Cells.
S. Esufali, G. S. Charames, V. V. Pethe, P. Buongiorno, and B. Bapat (2007)
Cancer Res. 67, 2469-2479
   Abstract »    Full Text »    PDF »
Wnt inhibitory factor inhibits lung cancer cell growth.
J. Kim, L. You, Z. Xu, K. Kuchenbecker, D. Raz, B. He, and D. Jablons (2007)
J. Thorac. Cardiovasc. Surg. 133, 733-737
   Abstract »    Full Text »    PDF »
The canonical Wnt signalling pathway and its APC partner in colon cancer development.
J. Schneikert and J. Behrens (2007)
Gut 56, 417-425
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Serial analysis of chromatin occupancy identifies beta-catenin target genes in colorectal carcinoma cells.
G. S. Yochum, S. McWeeney, V. Rajaraman, R. Cleland, S. Peters, and R. H. Goodman (2007)
PNAS 104, 3324-3329
   Abstract »    Full Text »    PDF »
Smad4 Regulates Claudin-1 Expression in a Transforming Growth Factor-{beta}-Independent Manner in Colon Cancer Cells.
S.-R. Shiou, A. B. Singh, K. Moorthy, P. K. Datta, M. K. Washington, R. D. Beauchamp, and P. Dhawan (2007)
Cancer Res. 67, 1571-1579
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Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis.
D. Dikovskaya, D. Schiffmann, I. P. Newton, A. Oakley, K. Kroboth, O. Sansom, T. J. Jamieson, V. Meniel, A. Clarke, and I. S. Nathke (2007)
J. Cell Biol. 176, 183-195
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