Wnt Signalling Pathway Parameters for Mammalian Cells

Tan, Chin Wee; Gardiner, Bruce S.; Hirokawa, Yumiko; Layton, Meredith J.; Smith, David W.; Burgess, Antony W.

doi:10.1371/journal.pone.0031882

Cited by 101 publications

(134 citation statements)

References 75 publications

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“…These observations suggest that other FAM83 members that also bind CK1α probably account for the enhanced nuclear pool of CK1α 31. Because most of the β‐catenin protein is reported to be associated with the plasma membrane 41, 42, we assessed the effect of PAWS1‐loss on membrane‐associated pool of β‐catenin. We also found high levels of total β‐catenin in the plasma membrane fractions and quite substantial amounts in the cytoskeletal fractions, when compared to cytoplasmic and nuclear fractions (Fig EV5E).…”

Section: Resultsmentioning

confidence: 99%

PAWS 1 controls Wnt signalling through association with casein kinase 1α

Bozatzi

Dingwell

et al. 2018

EMBO Reports

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The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co‐localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos.

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Section: Resultsmentioning

confidence: 99%

PAWS 1 controls Wnt signalling through association with casein kinase 1α

Bozatzi

Dingwell

et al. 2018

EMBO Reports

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“…In recent years, the association between catenin and cancer has become well known and the number of studies on the association between cell adhesion molecules and malignant behavior has increased (7,8). β-catenin is an important multifunctional cytoplasmic protein, which was initially considered as an intracellular molecule on the cell membrane that interacted with the calcium-dependent adhesion molecule E-cadherin (9).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of β-catenin by siRNA influences proliferation, apoptosis and invasion of the colon cancer cell line SW480

Zhou

et al. 2016

Oncology Letters

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Abstract. The aim of the present study was to explore the effect of knocking down the expression of β-catenin by small interference (si)RNA on the activity of the Wnt/β-catenin signaling pathway, and the proliferation, apoptosis and invasion abilities of the human colon cancer cell line SW480. For that purpose, double-stranded siRNA targeting β-catenin (β-catenin-siRNA) was synthesized and transfected into SW480 cells. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the messenger (m)RNA and protein levels of β-catenin in SW480 cells. To detect cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, while cell apoptosis and caspase-3 activity were detected by flow cytometry and caspase-3 activity assay, respectively. Matrigel invasion assay was performed to detect the influence of siRNA-mediated gene silencing on the invasion and metastasis of SW480 cells in vitro. The results of RT-PCR and western blot analysis demonstrated that, compared with the blank control, negative control and liposome groups, β-catenin-siRNA transfected SW480 cells had significantly decreased mRNA and protein levels of β-catenin. In addition, following β-catenin-siRNA transfection, the proliferation of SW480 cells was significantly lower than that of the blank control, negative control and liposome groups, while the apoptosis rate increased in β-catenin-siRNA transfected cells, compared with the aforementioned groups. Invasion assay showed that, following β-catenin-siRNA transfection, the number of SW480 cells infiltrating through the Matrigel membrane was significantly lower than that of the blank control, negative control and liposome groups. Following β-catenin-siRNA transfection, the caspase-3 activity in SW480 cells was lower than that in the blank control, negative control and liposome groups. These results indicate that siRNA-mediated silencing of β-catenin could inhibit the proliferation and invasion of SW480 cells and induce apoptosis, thus providing novel potential strategies for the clinical treatment of colon cancer, and may serve as a novel target for cancer therapy.

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“…Measurements of two mammalian kidney cell lines have shown that Axin concentrations are in the range 110 -150 nM; total and cytosolic b-catenin concentrations are in the hundreds and tens of nM range, respectively (Tan et al 2012). APC is found at 12 -40Â lower concentrations than Axin in these cells.…”

Section: E C I S S a M P K 2003 C H E E E E R P T N Y S I K Y N E E 1mentioning

confidence: 99%

“…However, the APC interaction mediated by the RGS domain is dispensable when Axin is overexpressed in SW480 colon cancer cells (see below) (Kohler et al 2009;Roberts et al 2011). Measurements of destruction complex components in mammalian kidney epithelial cells and Xenopus oocytes gave different absolute and relative concentrations of APC and Axin (Salic et al 2000;Lee et al 2003;Tan et al 2012), suggesting that Wnt signaling operates over a range of component concentrations that vary with cell type. Studies in Drosophila have suggested that precise APC levels are important in modulating Wnt responses; a twofold change in APC2 was shown to profoundly affect signaling in photoreceptor development, indicating that APC levels are likely tuned to optimize responses to morphogen gradients .…”

Section: Axin the Central Phosphorylation Scaffoldmentioning

confidence: 99%

The -Catenin Destruction Complex

Stamos

Weis

2012

Cold Spring Harbor Perspectives in Biology

893

783

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The Wnt/b-catenin pathway is highly regulated to insure the correct temporal and spatial activation of its target genes. In the absence of a Wnt stimulus, the transcriptional coactivator b-catenin is degraded by a multiprotein "destruction complex" that includes the tumor suppressors Axin and adenomatous polyposis coli (APC), the Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A (PP2A), and the E3-ubiquitin ligase b-TrCP. The complex generates a b-TrCP recognition site by phosphorylation of a conserved Ser/Thr-rich sequence near the b-catenin amino terminus, a process that requires scaffolding of the kinases and bcatenin by Axin. Ubiquitinated b-catenin is degraded by the proteasome. The molecular mechanisms that underlie several aspects of destruction complex function are poorly understood, particularly the role of APC. Here we review the molecular mechanisms of destruction complex function and discuss several potential roles of APC in b-catenin destruction.

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Wnt Signalling Pathway Parameters for Mammalian Cells

Cited by 101 publications

References 75 publications

PAWS 1 controls Wnt signalling through association with casein kinase 1α

PAWS 1 controls Wnt signalling through association with casein kinase 1α

Knockdown of β-catenin by siRNA influences proliferation, apoptosis and invasion of the colon cancer cell line SW480

The -Catenin Destruction Complex

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