Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC
            <sup>−/−</sup>
            Colon Carcinoma

Kor̆ínek, Vladimír; Barker, Nick; Morin, Patrice J.; Wichen, D van; Weger, Roel de; Kinzler, Kenneth W.; Vogelstein, Bert; Clevers, Hans

doi:10.1126/science.275.5307.1784

Cited by 3,065 publications

(2,617 citation statements)

References 17 publications

Supporting

Mentioning

2,512

Contrasting

Unclassified

Order By: Relevance

“…Lithium chloride (LiCl), which mimics Wnt signaling by inhibiting GSK-3b activity, was used as a positive control of nuclear b-catenin (van Noort et al, 2002). To confirm whether Id-1-induced nuclear b-catenin expression activates TCF/lymphoid enhancer factor (LEF) transcription activity, the promoter assay with TCF/ LEF promoter (TCF optimal promoter (TOP)) or its mutant form (fake optimal promoter) containing binding sites for Tcf4 (Korinek et al, 1997) was analysed. As shown in Figure 3d, TCF/LEF promoter activity was increased by Id-1 and strongly decreased upon Id-1 suppression by antisense construct (left).…”

Section: Id-1 Inhibits Pten Transcription Through P53 Downregulationmentioning

confidence: 99%

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

View full text Add to dashboard Cite

Inhibitor of differentiation-1 (Id-1) has been accepted as a putative oncogene to promote oncogenic processes through inactivation of tumor suppressors and activation of growth promoting pathways. Here, we show that Id-1 activates the Akt pathway by inhibition of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) transcription through downregulation of p53. Id-1 negatively regulated both p53 and PTEN at the transcriptional level. In promoter assay with serial deletion and chromatin immunoprecipitation assay, the binding of p53 to the PTEN promoter was reduced by Id-1, suggesting that Id-1 regulates PTEN transcription through its p53 modulation. This led to Akt phosphorylation at Ser473 and the activation of the Akt-mediated canonical Wnt signaling pathway. The glycogen synthase kinase-3b phosphorylation at Ser9, stabilization and nuclear localization of b-catenin, T-cell factor (TCF)/lymphoid enhancer factor transactivation activity and cyclin D1 expression were enhanced by Id-1. On the other hand, Akt-mediated p27 Kip1 phosphorylation at Thr157 and its cytosolic localization were also increased in Id-1 overexpressing MCF7 cells. In conclusion, our results disclose Id-1 as a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27 Kip1 phosphorylation and suggest that the oncogenic function of Id-1 may be partly attributed to its PTEN inhibition in human breast carcinogenesis.

show abstract

Section: Id-1 Inhibits Pten Transcription Through P53 Downregulationmentioning

confidence: 99%

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

View full text Add to dashboard Cite

show abstract

“…Such a two nucleotide substitution in the b-catenin/TCF binding site has previously been described to dramatically reduce b-catenin/TCF signal transduction. 38,39 The TCF-4 cDNA cloned into pCDNA3zeo expression vector and the DNTCF-4 expression vector (which lacks the b-catenin binding domain) were kindly provided by Dr. H. Clevers (University Hospital, Utrecht, The Netherlands). 38 The b-catenin expression vector (in pCDNA3) expresses a mutated form of b-catenin less susceptible to degradation and was kindly provided by Dr. K. Orford and Dr. S. Byers (Lombardi Cancer Center, Georgetown University, Washington DC).…”

Section: Plasmidsmentioning

confidence: 99%

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Mestdagt

Polette

Butticè

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

The loss of E-cadherin expression and the translocation of b-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, b-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the b-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/b-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with b-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against b-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the b-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression. ' 2005 Wiley-Liss, Inc.Key words: MCP-1; b-catenin; breast cancer Chemokines constitute a superfamily of proinflammatory cytokines that are implicated in tumour progression, modulating not only host tumour-specific immunological response but also angiogenesis or tumour cell invasion and proliferation. 1-3 Monocyte chemotactic protein-1 (MCP-1) or CCL2 is a CC-chemokine that specifically attracts monocytes and memory T cells. It has been particularly implicated in processes characterized by mononuclear cell infiltration including breast cancer. 4,5 In some models, MCP-1 has been shown to display an antitumoral effect. 6,7 Nevertheless, a large number of studies demonstrate that MCP-1 facilitates tumour progression through its ability to recruit stromal cells including tumour associated macrophages (TAMs) and endothelial cells. 7-10 A pro-angiogenic role of MCP-1 has been demonstrated in many systems, facilitating tumour growth and dissemination. 8,9,11,12 Moreover, a direct effect of MCP-1 on tumour cell migration in vitro has also been described. 13 Recently, Lebrecht et al. 14 have correlated an increased MCP-1 serum level with an advanced breast tumour stage and the presence of lymph node metastasis. In the same way, Amann et al. 15 reported a significant association between MCP-1 urinary levels and tumour stage and grade. They suggested a use of its urinary level as prognosis marker in bladder cancer. The correlation between MCP-1 expression and a poor prognosis was also demonstrated for the squamous cell carcinoma of the oeso...

show abstract

“…This complex allows the phosphorylation of b-catenin by GSK3, which targets b-catenin for degradation by the proteasome. In the absence of APC (or in the presence of Wnt signal), this destruction complex is dissociated and b-catenin accumulates and translocates into the nucleus, where it interacts with TCF/LEF transcription factors to drive transcription of TCF/LEF (or Wnt) target genes (Korinek et al, 1997).…”

mentioning

confidence: 99%

Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

Athineos

Sansom

2010

Oncogene

View full text Add to dashboard Cite

Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC ^−/− Colon Carcinoma

Cited by 3,065 publications

References 17 publications

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

Contact Info

Product

Resources

About

Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma

Cited by 3,065 publications

References 17 publications

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

Contact Info

Product

Resources

About

Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC ^−/− Colon Carcinoma