The significance of the Wnt pathway in the pathology of human cancers

Karim, Rooshdiya Z.; Tse, Gary M.; Putti, Thomas Choudary; Scolyer, Richard A.; Lee, C. Soon

doi:10.1080/00313020410001671957

Cited by 258 publications

(195 citation statements)

References 56 publications

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“…β-Catenin is an important intracellular glycoprotein that participates in cell adhesion and plays an important role in the Wnt signal transduction pathway. When cytoplasmic free β-catenin exceeds the APC degradation capacity, the redundant β-catenin enters the nucleus to activate the Wnt signalling pathway, initiates the transcription of target genes, such as c-myc, cyclinD1, and so on, and causes cell proliferation, invasion, and metastasis (Karim et al, 2004). Some reports found abnormal β-catenin expression in a wide variety of tumour; however, the expression rate in different tumours were also different (Ashibara et al, 2002;Ueta et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Axin and β-catenin Protein Expression in Primary Hepatocellular Carcinomas

Guan

Chen²,

Lou³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Clinical Significance of Axin and β-catenin Protein Expression in Primary Hepatocellular Carcinomas

Guan

Chen²,

Lou³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…10,11 An important and most studied Wnt pathway is the canonical Wnt signaling, which functions by modulating the translocation of b-catenin to the nucleus, where it controls critical gene expression programs via interaction with TCF/LEF and other families of transcription factors. In normal condition, casein kinase 1b (CK1b) and glycogen synthase kinase-3b (GSK-3b) sequentially phosphorylate b-catenin in the Axin complex, which is composed of the scaffolding protein Axin, the tumor suppressor adenomatous polyposis coli gene product (APC), CK1b, and GSK-3b.…”

Section: Introductionmentioning

confidence: 99%

Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathwayin vitroandin vivo

et al. 2015

Cancer Biology & Therapy

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Keywords: bladder cancer, HepaCAM, T24, Wnt/b-catenin Abbreviations: Ad, adenvirus; HepaCAM, hepatocyte cell adhesion molecule.We previously established that hepatocyte cell adhesion molecule (hepaCAM), a typical structure of immunoglobulin (Ig)-like adhesion molecules, inhibited the proliferation and the progression of cultured human bladder cancer cells. As increasing evidence reveals that aberrant activation of canonical Wnt pathway is involved in the pathogenesis of bladder cancer, and b-catenin serves as a pivotal molecule of Wnt pathway. Then, we explored whether the antiproliferation effect of hepaCAM was associated with Wnt/b-catenin pathway in human bladder cancer cells. The negative correlation between hepaCAM and b-catenin in transitional cell carcinoma of bladder (TCCB) was found. Follow by, studied the effect of hepaCAM on the key elements of Wnt pathway. Here, Our researches showed that hepaCAM played a central role in modulating the Wnt/b-catenin signaling pathway by interfering nuclear protein levels of b-catenin, leading to down-regulate transcriptional activity of LEF/TCF and its target genes c-Myc and cyclinD1. Mechanistically, we demonstrated that hepaCAM-activated GSK3b led to elevate the phosphorylation of b-catenin, contributing to the aberrant translocation of b-catenin. In addition, Anti-proliferation and associated molecular mechanisms of hepaCAM were demonstrated by using vivo experiment. In conclusion, our reports uncover that expression of hepaCAM suppresses the proliferation of bladder cancer cells through a Wnt/b-catenin-dependent signaling pathway in vitro and in vivo.

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“…14,15 Dysregulation of Wnt/b-catenin signaling facilitates cancer invasion and metastases in various tumours. 16,17 Inactive Wnt signaling results in cytoplasmic b-catenin associating with a multimolecular complex containing casein kinase a, glycogen synthase kinase-3b (GSK-3b), axin and adenomatosis polyposis coli (APC) protein. 15,16 This complex promotes phosphorylation of b-catenin leading to its ubiquitination and subsequent degradation by the proteasome.…”

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confidence: 99%

Characterization of Wnt/β-catenin signaling in rhabdomyosarcoma

Rao

Cialfi

Dominici

et al. 2013

Laboratory Investigation

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Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and accounts for about 5% of all malignant paediatric tumours. b-Catenin, a multifunctional nuclear transcription factor in the canonical Wnt signaling pathway, is active in myogenesis and embryonal somite patterning. Dysregulation of Wnt signaling facilitates tumour invasion and metastasis. This study characterizes Wnt/b-catenin signaling and functional activity in paediatric embryonal and alveolar RMS. Immunohistochemical assessment of paraffin-embedded tissues from 44 RMS showed b-catenin expression in 26 cases with cytoplasmic/membranous expression in 9/14 cases of alveolar RMS, and 15/30 cases of embryonal RMS, whereas nuclear expression was only seen in 2 cases of embryonal RMS. The potential functional significance of b-catenin expression was tested in four RMS cell lines, two derived from embryonal (RD and RD18) RMS and two from alveolar (Rh4 and Rh30) RMS. Western blot analysis demonstrated the expression of Wnt-associated proteins including b-catenin, glycogen synthase kinase-3b, disheveled, axin-1, naked, LRP-6 and cadherins in all cell lines. Cell fractionation and immunofluorescence studies of the cell lines (after stimulation by human recombinant Wnt3a) showed reduced phosphorylation of b-catenin, stabilization of the active cytosolic form and nuclear translocation of b-catenin. Reporter gene assay demonstrated a T-cell factor/lymphoid-enhancing factor-mediated transactivation in these cells. In response to human recombinant Wnt3a, the alveolar RMS cells showed a significant decrease in proliferation rate and induction of myogenic differentiation (myogenin, MyoD1 and myf5). These data indicate that the central regulatory components of canonical Wnt/b-catenin signaling are expressed and that this pathway is functionally active in a significant subset of RMS tumours and might represent a novel therapeutic target.

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The significance of the Wnt pathway in the pathology of human cancers

Cited by 258 publications

References 56 publications

Clinical Significance of Axin and β-catenin Protein Expression in Primary Hepatocellular Carcinomas

Clinical Significance of Axin and β-catenin Protein Expression in Primary Hepatocellular Carcinomas

Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathwayin vitroandin vivo

Characterization of Wnt/β-catenin signaling in rhabdomyosarcoma

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