P-cadherin and the journey to cancer metastasis

Molecular Cancer

Review

André Filipe Vieira¹  Joana Paredes² 

[1] Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;IPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho, N. 45, 4200-135, Porto, Portugal;Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;IPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho, N. 45, 4200-135, Porto, Portugal;Faculdade de Medicina da Universidade do Porto, Porto, Portugal;

关键词: P-cadherin;    Metastasis;    Cancer;    Cancer stem cells;    Invasion;   

DOI  :  10.1186/s12943-015-0448-4

 received in 2015-04-28, accepted in 2015-09-25,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Vieira and Paredes. 2015