β-Catenin hits chromatin: regulation of Wnt target gene activation

Mosimann, Christian; Hausmann, George; Basler, Konrad

doi:10.1038/nrm2654

Cited by 537 publications

(524 citation statements)

References 96 publications

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“…Activation of the Wnt signaling pathway and components of the pathway have been associated with cervical carcinoma (44), so it is not unreasonable to suggest that the activity of hPygo2 in cervical cancer and in cervical dysplasia which we report in this study, may be linked to, or be a prerequisite for Wnt signal transduction, given its role as a chromatin modifier in this context (45). Our recent findings (Andrews and colleagues, submitted), however, have shown an additional but strong requirement for malignant growth-associated ribosome biogenesis in HeLa cells, a cervical adenocarcinoma-derived cell line.…”

Section: Discussionmentioning

confidence: 94%

Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

Tzenov

Andrews

Voisey

et al. 2013

Molecular Cancer Research

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The human papillomavirus (HPV) is the etiologic agent of cervical cancer. In this study, we provide evidence for the human Pygopus (hPygo)2 gene as a cellular biomarker for HPV-related disease. In a tumor microarray of cervical cancer progression, hPygo2 levels were greater in high-grade lesions and squamous cell carcinomas than in normal epithelia. Similarly, hPygo2 mRNA and protein levels were greater in HPV-positive cervical cancer cells relative to uninfected primary cells. RNA interference (RNAi)-mediated depletion of HPV-E7 increased whereas E74-like factor (Elf)-1 RNAi decreased association of Retinoblastoma (Rb) tumor suppressor with the hPygo2 promoter in cervical cancer cell lines. Transfection of dominant-active Rb inhibited Elf-1-dependent activation of hPygo2, whereas Elf-1 itself increased hPygo2 expression. Chromatin immunoprecipitation assays showed that Rb repressed hPygo2 by inhibiting Elf-1 at the Ets-binding site in the hPygo2 promoter. These results suggested that abrogation of Rb by E7 resulted in derepression of Elf-1, which in turn stimulated expression of hPygo2.

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Section: Discussionmentioning

confidence: 94%

Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

Tzenov

Andrews

Voisey

et al. 2013

Molecular Cancer Research

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“…Together, these complexes act to induce expression of a cohort of genes including c-myc that influence proliferation and apoptosis (reviewed in Ref. 9 ).…”

Section: Confusing Wnt Terminologymentioning

confidence: 99%

When pathways collide: collaboration and connivance among signalling proteins in development

McNeill

Woodgett

2010

Nat Rev Mol Cell Biol

145

106

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Signal transduction pathways interact at various levels in defining tissue morphology, size and differentiation during development. Understanding of the mechanisms by which these pathways collude has been greatly enhanced by recent insights into how shared components are independently regulated and how the activity of one system is contextualized by others. Traditionally, the components of signalling pathways have been assumed to show pathway fidelity and to act with a high degree of autonomy. However, as illustrated by the Wnt and Hippo pathways, there is increasing evidence that components are often shared between multiple pathways and other components talk to each other through multiple mechanisms.

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“…APC is also crucial for capture of b-catenin in the degradation complex and it binds b-catenin directly via its centrally localized armadillo repeats (Xing et al, 2004). Upon Wnt activation, accumulated b-catenin enters the nucleus and binds to the TCF/LEF family transcriptional factors and induces the expression of its target genes (Moon et al, 2004;Mosimann et al, 2009). The key event of both Wnt signaling transduction and cancerous cell proliferation is the regulation of b-catenin stability and activity.…”

Section: Introductionmentioning

confidence: 99%

A Rac1/PAK1 cascade controls β-catenin activation in colon cancer cells

et al. 2011

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P21-activated kinase 1 (PAK1) is associated with colon cancer progression and metastasis, whereas the molecular mechanism remains elusive. Here, we show that downregulation of PAK1 in colon cancer cells reduces total b-catenin level, as well as cell proliferation. Mechanistically, PAK1 directly phosphorylates b-catenin proteins at Ser675 site and this leads to more stable and transcriptional active b-catenin. Corroborating these results, PAK1 is required for full Wnt signaling, and superactivation of b-catenin is achieved by simultaneous knockdown of adenomatous polyposis coli protein and activation of PAK1. Moreover, we show that Rac1 functions upstream of PAK1 in colon cancer cells and contributes to b-catenin phosphorylation and accumulation. We conclude that a Rac1/PAK1 cascade controls b-catenin S675 phosphorylation and full activation in colon cancer cells. Supporting this conclusion, overexpression of PAK1 is observed in 70% of colon cancer samples and is correlated with massive b-catenin accumulation.

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β-Catenin hits chromatin: regulation of Wnt target gene activation

Cited by 537 publications

References 96 publications

Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

When pathways collide: collaboration and connivance among signalling proteins in development

A Rac1/PAK1 cascade controls β-catenin activation in colon cancer cells

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