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Molecular Cancer

, 14:178

First Online: 06 October 2015Received: 28 April 2015Accepted: 25 September 2015DOI: 10.1186-s12943-015-0448-4

Cite this article as: Vieira, A.F. & Paredes, J. Mol Cancer 2015 14: 178. doi:10.1186-s12943-015-0448-4

Abstract

P-cadherin is a classical cell-to-cell adhesion molecule with a homeostatic function in several normal tissues. However, its behaviour in the malignant setting is notably dependent on the cellular context. In some tumour models, such as melanoma and oral squamous cell carcinoma, P-cadherin acts as a tumour suppressor, since its absence is associated with a more aggressive cancer cell phenotype; nevertheless, the overexpression of this molecule is linked to significant tumour promoting effects in the breast, ovarian, prostate, endometrial, skin, gastric, pancreas and colon neoplasms. Herein, we review the role of P-cadherin in cancer cell invasion, as well as in loco-regional and distant metastatic dissemination. We focus in P-cadherin signalling pathways that are activated to induce invasion and metastasis, as well as cancer stem cell properties. The signalling network downstream of P-cadherin is notably dependent on the cellular and tissue context and includes the activation of integrin molecules, receptor tyrosine kinases, small molecule GTPases, EMT transcription factors, and crosstalk with other cadherin family members. As new oncogenic molecular pathways mediated by P-cadherin are uncovered, putative therapeutic options can be tested, which will allow for the targeting of invasion or metastatic disease, depending on the tumour model.

KeywordsP-cadherin Metastasis Cancer Cancer stem cells Invasion Abbreviationsβctnβ-catenin

CSCCancer stem cell

EEMEctodermal dysplasia, ectrodactyly, and macular dystrophy

EGFREpidermal growth factor receptor

GnRHGonadotropin-releasing hormone

GnRHrGonadotropin-releasing hormone receptor

HJMDHypotrichosis with juvenile macular dystrophy

IGF-1RInsulin-like growth factor receptor

MAPMitogen-activated protein

MMPMatrix metalloproteinase

NONitric oxide

OSCCOral squamous cell carcinoma

p120ctnp120-catenin

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Author: André Filipe Vieira - Joana Paredes

Source: https://link.springer.com/







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