Expression Pattern of Wnt Signaling Components in the Adult Intestine

Gregorieff, Alex; Pinto, Daniel; Begthel, Harry; Destrée, Olivier; Kielman, Menno F.

doi:10.1053/j.gastro.2005.06.007

Cited by 167 publications

(214 citation statements)

References 66 publications

Supporting

Mentioning

198

Contrasting

Unclassified

Order By: Relevance

“…The localization of both Wnt3 and FZD7 proteins in transformed hepatocytes implies a possible autocrine or paracrine loop of β-catenin activation in HBVrelated HCC. In this regard, a recent study also revealed that both Wnt3 and FZD7 are highly expressed in Paneth cells located in the lower portions of intestinal crypts of the small intestine which is known to be a highly proliferative tissue [47]. Taken together, these findings support the idea that both Wnt3 and FZD7 may be important in cell proliferation and migration via activation of the canonical Wnt signaling cascade.…”

Section: Discussionsupporting

confidence: 64%

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Kim¹,

Lee²,

Tsedensodnom³

et al. 2008

Journal of Hepatology

171

173

View full text Add to dashboard Cite

Background/Aims-The canonical Wnt signaling is frequently activated in human hepatocellular carcinoma (HCC). We previously demonstrated that up-regulation of Frizzled-7 receptor (FZD7) in HCC was associated with nuclear accumulation of wild-type β-catenin. Here, we investigated Wnt ligand(s) that may activate the Wnt/β-catenin pathway through FZD7 in HCC cells. Results-In hepatitis B virus (HBV)-induced HCC, Wnt3 was upregulated in tumor and peritumoral tissues compared to normal liver and downstream β-catenin target genes were also increased in these samples. Activation of the Wnt/β-catenin pathway in FOCUS-Wnt3 cells was demonstrated by β-catenin accumulation, enhanced TCF transcriptional activity and proliferation rate. The activation of Wnt/β-catenin signaling in FOCUS-Wnt3 was abolished by a knockdown of FZD7 expression by siRNA. More important, a specific Wnt3-FZD7 interaction was observed by co-immunoprecipitation experiments, which suggest that the action of Wnt3 was mediated via FZD7. Methods-To identifyConclusions-These findings demonstrate a functional interaction between Wnt3 and FZD7 leading to activation of the Wnt/β-catenin signaling pathway in HCC cells and may play a role during hepatocarcinogenesis.

show abstract

Section: Discussionsupporting

confidence: 64%

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Kim¹,

Lee²,

Tsedensodnom³

et al. 2008

Journal of Hepatology

171

173

View full text Add to dashboard Cite

show abstract

“…Finally, to substantiate the responsiveness of these three miRNAs to dnTCF expression, we repeated the dox-dnTCF4 experiment and also included the previously described isogenic DLD1 cell line carrying doxinducible dnTCF1 alleles (van de Wetering et al, 2002) (Supplementary Figure S3). TCF1 and TCF4 have nearly identical binding affinities in vitro, but differ in their regulation-selectivity of specific loci and by their in vivo expression patterns (Waterman, 2004;Gregorieff et al, 2005;Medici et al, 2008). We also included the known growth-suppressive miR-145 and miR-126 miRNAs in the analysis, and found that all five miRNAs were upregulated to varying degrees following dnTCF1/4 expression although miR-30e-3p and miR-574-3p were preferentially regulated by dnTCF4 (Figure 2b).…”

Section: Resultsmentioning

confidence: 99%

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

et al. 2011

View full text Add to dashboard Cite

“…Sustained activation of the canonical Wnt pathway due to mutational deregulation of Wnt cascade components, such as APC, axin or b-catenin, is associated with several cancers (Lustig and Behrens, 2003;Gregorieff et al, 2005). Moreover, abnormal activation of the Wnt signalling pathway could be independent of Wnt component mutations (Bafico et al, 2004;Merle et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/β-catenin pathway

et al. 2009

View full text Add to dashboard Cite

The development of chemoresistance represents a major obstacle in the successful treatment of cancers such as neuroblastoma (NB), a particularly aggressive childhood solid tumour. The mechanisms underlying the chemoresistant phenotype in NB were addressed by gene expression profiling of two doxorubicin (DoxR)-resistant vs sensitive parental cell lines. Not surprisingly, the MDR1 gene was included in the identified upregulated genes, although the highest overexpressed transcript in both cell lines was the frizzled-1 Wnt receptor (FZD1) gene, an essential component of the Wnt/b-catenin pathway. FZD1 upregulation in resistant variants was shown to mediate sustained activation of the Wnt/b-catenin pathway as revealed by nuclear b-catenin translocation and target genes transactivation. Interestingly, specific microadapted short hairpin RNA (shRNAmir)-mediated FZD1 silencing induced parallel strong decrease in the expression of MDR1, another b-catenin target gene, revealing a complex, Wnt/b-catenin-mediated implication of FZD1 in chemoresistance. The significant restoration of drug sensitivity in FZD1-silenced cells confirmed the FZD1-associated chemoresistance. RNA samples from 21 patient tumours (diagnosis and postchemotherapy), showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/b-catenin pathway in clinical chemoresistance. Our data represent the first implication of the Wnt/b-catenin pathway in NB chemoresistance and identify potential new targets to treat aggressive and resistant NB.

show abstract

Expression Pattern of Wnt Signaling Components in the Adult Intestine

Abstract: Our study predicts a much broader role for Wnt signaling in gut development and homeostasis than was previously anticipated from available genetic studies and identifies novel factors likely involved in promoting canonical and noncanonical Wnt signals in the intestine.

Cited by 167 publications

References 66 publications

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/β-catenin pathway

Contact Info

Product

Resources

About