Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment
Thomas Brabletz,Andreas Jung,Simone Reu,Marc Porzner,Falk Hlubek,Leoni A. Kunz-Schughart,Ruth Knuechel,Thomas Kirchner +7 more
TLDR
It is postulate that an important driving force for progression of well-differentiated colorectal carcinomas is the specific environment, initiating two transient phenotypic transition processes by modulating intracellular β-catenin distribution in tumor cells.Abstract:
Invasion and dissemination of well-differentiated carcinomas are often associated with loss of epithelial differentiation and gain of mesenchyme-like capabilities of the tumor cells at the invasive front. However, when comparing central areas of primary colorectal carcinomas and corresponding metastases, we again found the same differentiated epithelial growth patterns. These characteristic phenotypic changes were associated with distinct expression patterns of β-catenin, the main oncogenic protein in colorectal carcinomas, and E-cadherin. Nuclear β-catenin was found in dedifferentiated mesenchyme-like tumor cells at the invasive front, but strikingly, as in central areas of the primary tumors, was localized to the membrane and cytoplasm in polarized epithelial tumor cells in the metastases. This expression pattern was accompanied by changes in E-cadherin expression and proliferative activity. On the basis of these data, we postulate that an important driving force for progression of well-differentiated colorectal carcinomas is the specific environment, initiating two transient phenotypic transition processes by modulating intracellular β-catenin distribution in tumor cells.read more
Citations
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References
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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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Identification of c-MYC as a Target of the APC Pathway
Tong-Chuan He,Andrew B. Sparks,Carlo Rago,Heiko Hermeking,Leigh Zawel,Luis T. da Costa,Patrice J. Morin,Bert Vogelstein,Kenneth W. Kinzler +8 more
TL;DR: The c-MYC oncogene is identified as a target gene in this signaling pathway and shown to be repressed by wild-type APC and activated by beta-catenin, and these effects were mediated through Tcf-4 binding sites in the c- MYC promoter.
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Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Patrice J. Morin,Andrew B. Sparks,Vladimir Korinek,Nick Barker,Hans Clevers,Bert Vogelstein,Kenneth W. Kinzler +6 more
TL;DR: Results indicate that regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or β- catenin.
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Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
Osamu Tetsu,Frank McCormick +1 more
TL;DR: It is shown that β-catenin activates transcription from the cyclin D1 promoter, and that sequences within the promoter that are related to consensus TCF/LEF-binding sites are necessary for activation.
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Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC−/− Colon Carcinoma
Vladimir Korinek,Nick Barker,Patrice J. Morin,Dick F. van Wichen,Roel A. de Weger,Kenneth W. Kinzler,Bert Vogelstein,Hans Clevers +7 more
TL;DR: Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.