P‐cadherin as a prognostic indicator and a modulator of migratory behaviour in bladder carcinoma cells

Mandeville, Jessica A.; Neto, Brasil Silva; Vanni, Alex J.; Smith, Gjanje; Rieger-Christ, Kimberly; Zeheb, Ron; Loda, Massimo; Libertino, John A.; Summerhayes, Ian C.

doi:10.1111/j.1464-410x.2008.08115.x

Cited by 36 publications

(46 citation statements)

References 28 publications

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“…Using in vitro breast cancer cell models, we found that overexpression of P-cadherin promotes single cell motility, directional cell migration, as well as invasion capacity through the matrigel matrix . This same migratory phenotype was observed in bladder, pancreatic and cholangiocarcinoma cancer cell lines (Baek et al, 2010, Mandeville et al, 2008, Taniuchi et al, 2005, Van Marck et al, 2011.…”

Section: P-cadherin Role In Adhesion Invasion and Motilitysupporting

confidence: 76%

“…On the other hand, in several other models, including breast cancer, P-cadherin behaves as an oncogene, and is often reported to correlate with increased tumour cell motility and invasiveness when aberrantly expressed (Cheung et al, 2010, Mandeville et al, 2008, Paredes et al, 2007a, Taniuchi et al, 2005, Van Marck et al, 2011. Using in vitro breast cancer cell models, we found that overexpression of P-cadherin promotes single cell motility, directional cell migration, as well as invasion capacity through the matrigel matrix .…”

Section: P-cadherin Role In Adhesion Invasion and Motilitymentioning

confidence: 57%

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P-cadherin role in normal breast development and cancer

Albergaria

Ribeiro²,

Vieira³

et al. 2011

Int. J. Dev. Biol.

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P-cadherin is a cell-cell adhesion molecule, whose expression is highly associated with undifferentiated cells in normal adult epithelial tissues, as well as with poorly differentiated carcinomas. Its expression has been already reported in human embryonic stem cells and it is presumed to be a marker of stem or progenitor cells of some epithelial tissues. In normal breast, P-cadherin has an essential role during ductal mammary branching, being expressed by the monolayer of epithelial cap cells at the end buds. In mature mammary tissue, its expression is restricted to the myoepithelium; it has been postulated that it may also be present in early luminal progenitor cells. In breast cancer, P-cadherin is frequently overexpressed in high-grade tumours, being a well-established indicator of poor patient prognosis. It has been reported as an important inducer of cancer cell migration and invasion, with underlying molecular mechanisms involving the signalling mediated by its juxtamembrane domain, the secretion of matrix metalloproteases to the extracellular media, and the cleavage of a P-cadherin soluble form with pro-invasive activity. Intracellularly, this protein interferes with the endogenous cadherin/catenin complex, inducing p120-catenin delocalization to the cytoplasm, and the consequent activation of Rac1/Cdc42 and associated alterations in the actin cytoskeleton. Considering P-cadherin's role in cancer cell invasion and metastasis formation, a humanized monoclonal antibody was recently produced to antagonize P-cadherin-associated signalling pathways, which is currently under Phase I clinical trials. In this review, the most important findings about the role of P-cadherin in normal breast development and cancer will be illustrated and discussed, with emphasis on the most recent data.

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Section: P-cadherin Role In Adhesion Invasion and Motilitysupporting

confidence: 76%

Section: P-cadherin Role In Adhesion Invasion and Motilitymentioning

confidence: 57%

P-cadherin role in normal breast development and cancer

Albergaria

Ribeiro²,

Vieira³

et al. 2011

Int. J. Dev. Biol.

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“…In contrast Mandeville et al found positive membranous P-cadherin immunostaining in the basal layer of normal urothelium. As in normal bladder urothelium, superficial tumors expressed P-cadherin, whereas 50% of muscle-invasive cancers were P-cadherin-negative (25). Furthermore, high P-cadherin gene expression proved to be an independent favorable prognostic factor of cancer-related survival (HR, 0.391; 95% CI, 0.196-0.780; P=0.008) and a risk factor of recurrence in superficial cancers after tumor resection (P=0.020).…”

Section: Discussionmentioning

confidence: 93%

“…In contrast, low P-cadherin level reported to be a favorable prognostic factor in breast and in endometrial cancer (22,23). The two recent immunohistochemical studies dealing with this issue reported contrary results regarding both expression patterns in different tumor stages and prognostic role of P-cadherin (24,25).…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of cadherin switch in bladder cancer

et al. 2010

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Abstract.Loss of E-cadherin expression and gain of Ncadherin expression ('cadherin switch') is shown to be characteristic in epithelial to mesenchymal transition (EMT), a mechanism associated with cancer progression. Furthermore, the prognostic role of P-cadherin in different cancers is controversial. The aim of this study was to evaluate the prognostic significance of 'cadherin switch' on the gene expression level in bladder cancer. Frozen tissue samples of 181 bladder cancer patients and 7 control individuals were analyzed by quantitative real-time PCR. Kaplan-Meier logrank test and Cox univariate and multivariate analysis were performed to assess the prognostic relevance of gene expression of E-, N-and P-cadherin. Cox univariate analysis revealed that the decrease of E-cadherin and the gain of Ncadherin gene expression are risk factors for cancer-related death (P=0.087, P=0.005, respectively). Fourteen percent (13/92) of muscle-invasive bladder cancers were N-cadherinnegative. These patients had a significantly poorer prognosis than those with N-cadherin-positive muscle-invasive tumors (P=0.024). P-cadherin gene expression proved to be a significant independent prognostic factor for both cancerspecific and recurrence-free survival (P=0.011, P=0.036). The characteristic 'cadherin switch' between low-and high-stage tumors that we observed and the prognostic significance of E-, N-and P-cadherin suggests the importance of these markers in bladder cancer progression. The poor patient prognosis in N-cadherin-negative muscle-invasive tumors indicates an alternative, N-cadherin-independent way in bladder cancer progression.

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“…Decreased E-cadherin immune-reactivity was first described in bladder cancer in 1993 15 . A number of studies then followed, which demonstrated cadherin switching in the setting of bladder cancer, associated with late stage, high grade disease 9,[16][17][18][19] . A detailed study using on cadherin switching using pT1 and T2-T3 bladder tumours 19 demonstrated that N-Cadherin expressing bladder cancer progressed more rapidly, and the majority of T2-T3 tumours demonstrated no expression of E-cadherin.…”

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confidence: 99%

PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells

Ismail

Halaçlı

Babteen

et al. 2017

Biochemical Journal

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Urothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150,000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long term prognosis. Thus there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down regulation of E-cadherin expression concomitant with a suppression of cell: cell junctions and decreased levels of E-cadherin expression have been reported in higher grade urothelial bladder tumours. We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell: cell junctions and the level of PAK5 expression. Interestingly exogenous PAK5 has recently been described to be associated with cell: cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that in both our own patient samples and a commercially available datasets that PAK5mRNA levels are reduced in human bladder cancer compared to normal controls. Taken together this study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression. PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells AbstractUrothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150,000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long term prognosis. Thus there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down regulation of E-cadherin expression concomitant with a suppression of cell: cell junctions and decreased levels of Ecadherin expression have been reported in higher grade urothelial bladder tumours.We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell: cell junctions and the level of PAK5 expression.Interestingly exogenous PAK5 has recently been described to be associated with cell: cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that in both our own patient samples and a commercially available datasets that PAK5mRNA levels are reduced in human bladder c...

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P‐cadherin as a prognostic indicator and a modulator of migratory behaviour in bladder carcinoma cells

Cited by 36 publications

References 28 publications

P-cadherin role in normal breast development and cancer

P-cadherin role in normal breast development and cancer

The prognostic value of cadherin switch in bladder cancer

PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells

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