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Tumor progression induced by the loss of E-cadherin independent of beta-catenin/Tcf-mediated Wnt signaling

Herzig, M.; Savarese, F.; Novatchkova, M.; Semb, Henrik LU and Christofori, G (2007) In Oncogene 26(16). p.2290-2298
Abstract
E-cadherin-mediated cell-cell adhesion is frequently lost during the development of malignant epithelial cancers. Employing a transgenic mouse model of beta-cell carcinogenesis (Rip1Tag2) we have previously shown that the loss of E-cadherin is a rate-limiting step in the progression from adenoma to carcinoma. However, the mere loss of cell adhesion may not be sufficient and additional signals are required to cause tumor cells to permeate the basal membrane and to invade surrounding tissue. Besides being an important component of the E-cadherin cell-adhesion complex, beta-catenin plays a critical role in canonical Wnt signaling. We report here that beta-catenin-mediated Wnt signaling does not contribute to tumor progression in Rip1Tag2... (More)
E-cadherin-mediated cell-cell adhesion is frequently lost during the development of malignant epithelial cancers. Employing a transgenic mouse model of beta-cell carcinogenesis (Rip1Tag2) we have previously shown that the loss of E-cadherin is a rate-limiting step in the progression from adenoma to carcinoma. However, the mere loss of cell adhesion may not be sufficient and additional signals are required to cause tumor cells to permeate the basal membrane and to invade surrounding tissue. Besides being an important component of the E-cadherin cell-adhesion complex, beta-catenin plays a critical role in canonical Wnt signaling. We report here that beta-catenin-mediated Wnt signaling does not contribute to tumor progression in Rip1Tag2 mice. E-cadherin downregulates beta-catenin/Tcf-mediated transcriptional activity by sequestrating beta-catenin into E-cadherin cell-adhesion complexes even in the presence of activated Wnt signaling. Upon loss of E-cadherin expression, beta-catenin is degraded and Tcf/beta-catenin-mediated transcriptional activity is not induced. Moreover, forced expression of constitutive-active beta-catenin or genetic ablation of Tcf/beta-catenin transcriptional activity in tumor cells of Rip1Tag2 transgenic mice does not affect tumor progression. Together, the data indicate that signals other than beta-catenin/Tcf-mediated Wnt signaling are induced by the loss of E-cadherin during tumor progression in Rip1Tag2 transgenic mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
tumorigenesis, Tcf, E-cadherin, beta-catenin, cell adhesion, Wnt, signaling
in
Oncogene
volume
26
issue
16
pages
2290 - 2298
publisher
Nature Publishing Group
external identifiers
  • wos:000245466000005
  • scopus:34147093740
ISSN
1476-5594
DOI
10.1038/sj.onc.1210029
language
English
LU publication?
yes
id
0a51f520-a6cc-48b7-9299-4f7d2c014365 (old id 667282)
date added to LUP
2007-12-12 13:44:35
date last changed
2017-10-22 03:51:23
@article{0a51f520-a6cc-48b7-9299-4f7d2c014365,
  abstract     = {E-cadherin-mediated cell-cell adhesion is frequently lost during the development of malignant epithelial cancers. Employing a transgenic mouse model of beta-cell carcinogenesis (Rip1Tag2) we have previously shown that the loss of E-cadherin is a rate-limiting step in the progression from adenoma to carcinoma. However, the mere loss of cell adhesion may not be sufficient and additional signals are required to cause tumor cells to permeate the basal membrane and to invade surrounding tissue. Besides being an important component of the E-cadherin cell-adhesion complex, beta-catenin plays a critical role in canonical Wnt signaling. We report here that beta-catenin-mediated Wnt signaling does not contribute to tumor progression in Rip1Tag2 mice. E-cadherin downregulates beta-catenin/Tcf-mediated transcriptional activity by sequestrating beta-catenin into E-cadherin cell-adhesion complexes even in the presence of activated Wnt signaling. Upon loss of E-cadherin expression, beta-catenin is degraded and Tcf/beta-catenin-mediated transcriptional activity is not induced. Moreover, forced expression of constitutive-active beta-catenin or genetic ablation of Tcf/beta-catenin transcriptional activity in tumor cells of Rip1Tag2 transgenic mice does not affect tumor progression. Together, the data indicate that signals other than beta-catenin/Tcf-mediated Wnt signaling are induced by the loss of E-cadherin during tumor progression in Rip1Tag2 transgenic mice.},
  author       = {Herzig, M. and Savarese, F. and Novatchkova, M. and Semb, Henrik and Christofori, G},
  issn         = {1476-5594},
  keyword      = {tumorigenesis,Tcf,E-cadherin,beta-catenin,cell adhesion,Wnt,signaling},
  language     = {eng},
  number       = {16},
  pages        = {2290--2298},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Tumor progression induced by the loss of E-cadherin independent of beta-catenin/Tcf-mediated Wnt signaling},
  url          = {http://dx.doi.org/10.1038/sj.onc.1210029},
  volume       = {26},
  year         = {2007},
}