Aberrant Wnt/β-catenin signaling can induce chromosomal instability in colon cancer

Hadjihannas, Michel V.; Brückner, Martina K.; Jerchow, Boris; Birchmeier, Walter; Dietmaier, Wolfgang; Behrens, Jürgen

doi:10.1073/pnas.0604206103

Cited by 140 publications

(112 citation statements)

References 46 publications

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“…Importantly, such high ABI were reversed when the cells were introduced with dominant-negative TCF constructs, indicating that transcriptional activation was responsible (Aoki et al, 2006). Consistent with our observation, it has been shown that Wnt signaling causes CIN via upregulation of conductin (axin2) (Hadjihannas et al, 2006).…”

Section: Modifier Genes Of Apc Intestinal Polyposissupporting

confidence: 88%

Wnt signaling and gastrointestinal tumorigenesis in mouse models

Taketo

2006

Oncogene

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The canonical Wnt signaling plays important roles in embryonic development and tumorigenesis. For the latter, induced mutations in mice have greatly contributed to our understanding of the molecular mechanisms of cancer initiation and progression. Here, I will review recent reports on gastrointestinal cancer model mice, with an emphasis on the roles of the Wnt signal pathway. They include: mouse models for familial adenomatous polyposis; modifying factors that affect mouse intestinal polyposis, including the genes that help cancer progression; Wnt target genes that affect mouse intestinal polyposis; and a mouse model of gastric cancer that mimics Helicobacter pyroli infection.

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Section: Modifier Genes Of Apc Intestinal Polyposissupporting

confidence: 88%

Wnt signaling and gastrointestinal tumorigenesis in mouse models

Taketo

2006

Oncogene

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“…We discovered that in colorectal cancer cells, conductin localizes on the mitotic spindles and at centrosomes and that it forms protein complexes with the mitotic and spindle checkpoint regulator polo-like kinase 1 (PLK1). 43 In addition, we found that conductin suppresses the activity of the spindle checkpoint induced by microtubule disruption. This appears to depend on PLK1, since conductin can not reverse mitotic arrest caused by the polo box domain (PBD) of PLK1, which activates the spindle checkpoint by displacing…”

Section: Wnt/β-catenin Signaling Conductin and Cinmentioning

confidence: 77%

CIN by WNT: Growth Pathways, Mitotic Control and Chromosomal Instability in Cancer

Hadjihannas

Behrens²

2006

Cell Cycle

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“…Axin2 (also known as conductin) is highly up-regulated in the majority of colorectal tumors [21] and localizes to the mitotic spindles and centrosomes where it forms protein complexes with the mitotic and spindle checkpoint regulator polo-like kinase 1 (PLK1). Knock-down of Axin2 by siRNA in colon carcinoma cells or gene ablation in mouse embryo fibroblasts allows over-activation of the spindle checkpoint in response to spindle stress [36]. By contrast, activated Wnt signaling stimulates the APC or β-catenin mutant cells to escape from mitotic arrest and apoptosis [37].…”

Section: Discussionmentioning

confidence: 99%

A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/β-catenin signaling and colon cancer cell tumorigenesis

et al. 2011

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The Wnt/β-catenin signaling pathway is a highly conserved pathway in organism evolution and regulates many biological processes. Aberrant activation of the Wnt/β-catenin signaling pathway is closely related to tumorigenesis. In order to identify potent small molecules to treat the over-activated Wnt signaling-mediated cancer, such as colon cancer, we established a mammalian cell line-based reporter gene screening system. The screen revealed a diterpenoid derivative, 15-oxospiramilactone (NC043) that inhibits Wnt3a or LiCl-stimulated Top-flash reporter activity in HEK293T cells and growth of colon cancer cells, SW480 and Caco-2. Treatment of SW480 cells with NC043 led to decreases in the mRNA and/or protein expression of Wnt target genes Axin2, Cyclin D1 and Survivin, as well as decreases in the protein levels of Cdc25c and Cdc2. NC043 did not affect the cytosol-nuclear distribution and protein level of soluble β-catenin, but decreased β-catenin/TCF4 association in SW480 cells. Moreover, NC043 inhibited anchorage-independent growth and xenograft tumorigenesis of SW480 cells. Collectively these results demonstrate that NC043 is a novel small molecule that inhibits canonical Wnt signaling downstream of β-catenin stability and may be a potential compound for treating colorectal cancer.

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Aberrant Wnt/β-catenin signaling can induce chromosomal instability in colon cancer

Cited by 140 publications

References 46 publications

Wnt signaling and gastrointestinal tumorigenesis in mouse models

Wnt signaling and gastrointestinal tumorigenesis in mouse models

CIN by WNT: Growth Pathways, Mitotic Control and Chromosomal Instability in Cancer

A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/β-catenin signaling and colon cancer cell tumorigenesis

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