P-Cadherin Promotes Cell-Cell Adhesion and Counteracts Invasion in Human Melanoma

Stove, Christophe; Bossche, Karolien Van Den; Stove, Veronique; Paredes, Joana; Haeghen, Yves Vander; Bracke, Marc

doi:10.1158/0008-5472.can-04-4414

Cited by 91 publications

(83 citation statements)

References 48 publications

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“…In contrast, in highly invasive melanoma cell lines, P-cadherin overexpression is able to promote the formation of cell-cell contacts and counteract invasion (Van Marck et al, 2005), showing that it may function either as an invasion promoter or as an invasion suppressor depending on tissue specificity. On the basis of clinical evidences and on its contradictory biological role in distinct tumour tissues, we aimed at understanding how P-cadherin influences tumour aggressiveness.…”

Section: Discussionmentioning

confidence: 96%

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

et al. 2009

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Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.

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Section: Discussionmentioning

confidence: 96%

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

et al. 2009

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“…P-cadherin is also expressed in normal melanocytes and also likely plays a role in regulating regular cell-cell interactions between melanocytes and their surrounding cells (33). The down-regulation of either E-cadherin or P-cadherin, or the induction of N-cadherin, facilitates melanoma cell migration and invasion in in vitro assays (34)(35)(36). In this analysis, we report on the relevance of protein expression levels for E-cadherin, P-cadherin, and N-cadherin and for a-catenin, h-catenin, and p120-catenin, intracellular signal transducers of these cadherins to both melanoma progression and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Cadherin-Based Adhesion Molecules in Cutaneous Malignant Melanoma

Kreizenbeck¹,

Berger²,

Subtil³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: The need for novel molecular prognostic markers that can supplement validated clinicopathologic correlates for cutaneous malignant melanoma is well recognized. Proteins that mediate the epithelialmesenchymal transition, the process by which a cancer cell disengages from its parent tumor, are important candidates. Methods: The prognostic relevance of E-cadherin, N-cadherin, and P-cadherin, calcium-dependent transmembrane glycoproteins that regulate cell-cell adhesion, and their adaptors, A-catenin, B-catenin, and p120-catenin, was evaluated on a cohort of 201 primary and 274 metastatic melanoma tumors using fluorescencebased immunohistochemical methods and Automated Quantitative Analysis of protein expression on digitally captured photomicrographs. Results: Increasing levels of N-cadherin expression improved overall survival (log-rank = 7.31; P = 0.03) but did not retain significance following adjustment for established clinicopathologic correlates (P = 0.50). Higher levels of E-cadherin approached significance for favorable prognosis on both univariate (P = 0.13)

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“…Also, in melanomas, Pcadherin behaves as an invasion suppressor gene. Indeed, in highly invasive melanoma cell lines (that lack E-cadherin expression), P-cadherin overexpression was able to promote the formation of cell-cell contacts and counteract invasion (Van Marck et al, 2005). The anti-invasive effect of P-cadherin was also recently confirmed in in vivo experiments, showing that its expression is refractory to invasive signals induced by myofibroblasts.…”

Section: P-cadherin Role In Adhesion Invasion and Motilitymentioning

confidence: 91%

“…Although E-cadherin-induced signalling pathways have been extensively studied in cancer, little is known about the role of Pcadherin , Taniuchi et al, 2005, Van Marck et al, 2005. It is some kind expected that P-cadherin share common signalling pathways with other cadherins, due to its function as a cell-cell adhesion molecule; however, it is not known whether the pathways are triggered in the same way.…”

Section: P-cadherin-downstream Signalling Pathwaysmentioning

confidence: 99%

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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P-Cadherin Promotes Cell-Cell Adhesion and Counteracts Invasion in Human Melanoma

Cited by 91 publications

References 48 publications

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

Prognostic Significance of Cadherin-Based Adhesion Molecules in Cutaneous Malignant Melanoma

P-cadherin role in normal breast development and cancer

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