CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Caca, K.
Right arrow Articles by Fearon, E. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Caca, K.
Right arrow Articles by Fearon, E. R.
Cell Growth & Differentiation Vol. 10, 369-376, June 1999
© 1999 American Association for Cancer Research

ß- and {gamma}-Catenin Mutations, but not E-Cadherin Inactivation, Underlie T-Cell Factor/Lymphoid Enhancer Factor Transcriptional Deregulation in Gastric and Pancreatic Cancer1

Karel Caca2,, 3, Frank T. Kolligs2, Xiaodong Ji, Marianne Hayes, Jia-ming Qian4, Alan Yahanda, David L. Rimm, Jose Costa and Eric R. Fearon5

Departments of Internal Medicine [K. C., F. T. K., X. J., M. H., J-m. Q., E. R. F.], Surgery [A. Y.], Human Genetics [E. R. F.], and Pathology [E. R. F.], The Cancer Center and the Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109; and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510 [D. L. R., J. C.]

Adenomatous polyposis coli (APC) mutations are present in >70% of colon cancers. The APC protein binds to ß-catenin (ß-cat), a protein first identified because of its role in E-cadherin (E-cad) cell adhesion. In some colon cancers lacking APC defects, mutations in presumptive glycogen synthase kinase 3ß phosphorylation sites near the ß-cat NH2 terminus appear to render ß-cat resistant to regulation by APC and glycogen synthase kinase 3ß. In cells with APC or ß-cat defects, ß-cat is stabilized and, in turn, binds to and activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef) transcription factors. To further explore the role of APC, ß-cat, Tcf, and E-cad defects in gastrointestinal cancers, we assessed gastric and pancreatic cancers for constitutive Tcf transcriptional activity (CTTA). Two of four gastric and two of eight pancreatic cancer lines showed CTTA. One gastric and one pancreatic cancer had mutations in the NH2-terminal phosphorylation sites of ß-cat. The other gastric cancer with CTTA had a missense mutation at serine 28 of {gamma}-cat, a potential phosphorylation site in this ß-cat-related protein. Although E-cad is an important binding partner for ß-cat and {gamma}-cat, E-cad inactivation did not result in CTTA. The ß-cat and {gamma}-cat mutant proteins identified in our studies strongly activated Tcf transcription in vitro, whereas ß-cat mutant proteins with large NH2-terminal deletions had only modest effects on Tcf. Our results suggest a role for Tcf deregulation in gastric and pancreatic cancer, resulting from ß-cat and {gamma}-cat mutations in some cases and, in others, from yet to be defined defects. Furthermore, these data imply that the consequences of APC and ß-cat mutations are distinct from the effects of E-cad inactivation.




This article has been cited by other articles:


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
R. Di Liddo, T. Bertalot, A. Schuster, S. Schrenk, O. Müller, J. Apfel, P. Reischmann, S. Rajendran, R. Sfriso, M. Gasparella, et al.
Fluorescence-based gene reporter plasmid to track canonical Wnt signaling in ENS inflammation
Am J Physiol Gastrointest Liver Physiol, March 15, 2016; 310(6): G337 - G346.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
L. S. Besnier, P. Cardot, B. Da Rocha, A. Simon, D. Loew, C. Klein, B. Riveau, M. Lacasa, C. Clair, M. Rousset, et al.
The cellular prion protein PrPc is a partner of the Wnt pathway in intestinal epithelial cells
Mol. Biol. Cell, September 15, 2015; 26(18): 3313 - 3328.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. K. Bailey, M. K. Mittal, S. Misra, and G. Chaudhuri
High Motility of Triple-negative Breast Cancer Cells Is Due to Repression of Plakoglobin Gene by Metastasis Modulator Protein SLUG
J. Biol. Chem., June 1, 2012; 287(23): 19472 - 19486.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. Pelz, S. Steininger, C. Weiss, F. Coscia, and R. Vogelmann
A Novel Inhibitory Domain of Helicobacter pylori Protein CagA Reduces CagA Effects on Host Cell Biology
J. Biol. Chem., March 18, 2011; 286(11): 8999 - 9008.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
L. Grumolato, G. Liu, P. Mong, R. Mudbhary, R. Biswas, R. Arroyave, S. Vijayakumar, A. N. Economides, and S. A. Aaronson
Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors
Genes & Dev., November 15, 2010; 24(22): 2517 - 2530.
[Abstract] [Full Text] [PDF]


Home page
Cold Spring Harb. Perspect. Biol.Home page
P. D. McCrea, D. Gu, and M. S. Balda
Junctional Music that the Nucleus Hears: Cell-Cell Contact Signaling and the Modulation of Gene Activity
Cold Spring Harb Perspect Biol, October 1, 2009; 1(4): a002923 - a002923.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
K. Oguma, H. Oshima, M. Aoki, R. Uchio, K. Naka, S. Nakamura, A. Hirao, H. Saya, M. M. Taketo, and M. Oshima
Activated macrophages promote Wnt signalling through tumour necrosis factor-{alpha} in gastric tumour cells
EMBO J., June 18, 2008; 27(12): 1671 - 1681.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
K. Ganesan, T. Ivanova, Y. Wu, V. Rajasegaran, J. Wu, M. H. Lee, K. Yu, S. Y. Rha, H. C. Chung, B. Ylstra, et al.
Inhibition of Gastric Cancer Invasion and Metastasis by PLA2G2A, a Novel {beta}-Catenin/TCF Target Gene
Cancer Res., June 1, 2008; 68(11): 4277 - 4286.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
A. Salim and L. Ratner
Modulation of {beta}-Catenin and E-Cadherin Interaction by Vpu Increases Human Immunodeficiency Virus Type 1 Particle Release
J. Virol., April 15, 2008; 82(8): 3932 - 3938.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
J. M. Winter, A. H. Ting, F. Vilardell, E. Gallmeier, S. B. Baylin, R. H. Hruban, S. E. Kern, and C. A. Iacobuzio-Donahue
Absence of E-Cadherin Expression Distinguishes Noncohesive from Cohesive Pancreatic Cancer
Clin. Cancer Res., January 15, 2008; 14(2): 412 - 418.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
H. Dvory-Sobol, E. Sagiv, D. Kazanov, A. Ben-Ze'ev, and N. Arber
Targeting the active {beta}-catenin pathway to treat cancer cells.
Mol. Cancer Ther., November 1, 2006; 5(11): 2861 - 2871.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
H. Andersen, J. Mejlvang, S. Mahmood, I. Gromova, P. Gromov, E. Lukanidin, M. Kriajevska, J. K. Mellon, and E. Tulchinsky
Immediate and Delayed Effects of E-Cadherin Inhibition on Gene Regulation and Cell Motility in Human Epidermoid Carcinoma Cells
Mol. Cell. Biol., October 15, 2005; 25(20): 9138 - 9150.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
K S Nair, R Naidoo, and R Chetty
Expression of cell adhesion molecules in oesophageal carcinoma and its prognostic value
J. Clin. Pathol., April 1, 2005; 58(4): 343 - 351.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
H. Shiina, J. E. Breault, W. W. Basset, H. Enokida, S. Urakami, L.-C. Li, S. T. Okino, M. Deguchi, M. Kaneuchi, M. Terashima, et al.
Functional Loss of the {gamma}-Catenin Gene through Epigenetic and Genetic Pathways in Human Prostate Cancer
Cancer Res., March 15, 2005; 65(6): 2130 - 2138.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
C. J. Gottardi and B. M. Gumbiner
Distinct molecular forms of {beta}-catenin are targeted to adhesive or transcriptional complexes
J. Cell Biol., October 25, 2004; 167(2): 339 - 349.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. M. Al-Aynati, N. Radulovich, R. H. Riddell, and M.-S. Tsao
Epithelial-Cadherin and {beta}-Catenin Expression Changes in Pancreatic Intraepithelial Neoplasia
Clin. Cancer Res., February 15, 2004; 10(4): 1235 - 1240.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
H. Posthaus, L. Williamson, D. Baumann, R. Kemler, R. Caldelari, M. M. Suter, H. Schwarz, and E. Muller
{beta}-Catenin is not required for proliferation and differentiation of epidermal mouse keratinocytes
J. Cell Sci., December 1, 2002; 115(23): 4587 - 4595.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
M. Shtutman, J. Zhurinsky, M. Oren, E. Levina, and A. Ben-Ze'ev
PML Is a Target Gene of {beta}-Catenin and Plakoglobin, and Coactivates {beta}-Catenin-mediated Transcription
Cancer Res., October 15, 2002; 62(20): 5947 - 5954.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
D. A. Tice, I. Soloviev, and P. Polakis
Activation of the Wnt Pathway Interferes with Serum Response Element-driven Transcription of Immediate Early Genes
J. Biol. Chem., February 22, 2002; 277(8): 6118 - 6123.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
R. Wu, Y. Zhai, E. R. Fearon, and K. R. Cho
Diverse Mechanisms of {beta}-Catenin Deregulation in Ovarian Endometrioid Adenocarcinomas
Cancer Res., November 1, 2001; 61(22): 8247 - 8255.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
H. Roh, D. W. Green, C. B. Boswell, J. A. Pippin, and J. A. Drebin
Suppression of {beta}-Catenin Inhibits the Neoplastic Growth of APC-Mutant Colon Cancer Cells
Cancer Res., September 1, 2001; 61(17): 6563 - 6568.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
S. Chen, D. C. Guttridge, Z. You, Z. Zhang, A. Fribley, M. W. Mayo, J. Kitajewski, and C.-Y. Wang
WNT-1 Signaling Inhibits Apoptosis by Activating {beta}-Catenin/T Cell Factor-Mediated Transcription
J. Cell Biol., January 8, 2001; 152(1): 87 - 96.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
M. van de Wetering, N. Barker, I. C. Harkes, M. van der Heyden, N. J. Dijk, A. Hollestelle, J. G. M. Klijn, H. Clevers, and M. Schutte
Mutant E-cadherin Breast Cancer Cells Do Not Display Constitutive Wnt Signaling
Cancer Res., January 1, 2001; 61(1): 278 - 284.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
J. Zhurinsky, M. Shtutman, and A. Ben-Ze'ev
Plakoglobin and beta-catenin: protein interactions, regulation and biological roles
J. Cell Sci., September 15, 2000; 113(18): 3127 - 3139.
[Abstract] [PDF]


Home page
Genes Dev.Home page
F. T. Kolligs, B. Kolligs, K. M. Hajra, G. Hu, M. Tani, K. R. Cho, and E. R. Fearon
gamma -Catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta -catenin
Genes & Dev., June 1, 2000; 14(11): 1319 - 1331.
[Abstract] [Full Text]


Home page
JCOHome page
K. H. Goss and J. Groden
Biology of the Adenomatous Polyposis Coli Tumor Suppressor
J. Clin. Oncol., May 9, 2000; 18(9): 1967 - 1979.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.