Literature DB >> 25773677

Protease-activated receptor 2 enhances renal cell carcinoma cell invasion and migration via PI3K/AKT signaling pathway.

Zhixia Sun1, Bo Cao2, Jinsheng Wu3.   

Abstract

Protease-activated receptor 2 (PAR-2) has been implicated in the regulation of several cellular functions in the progression of cancer. It is reported that PAR-2 expression is significantly increased in human renal cell carcinoma (RCC) tissue compared with the adjacent non-neoplastic kidney tissue. However, the function of PAR-2 in regulating cell invasion and migration of RCC remains elusive. In this study, we found that PAR-2 was overexpressed in RCC cells. Activation of PAR-2 with PAR-2AP (PAR-2 agonist) enhanced the invasion and migration of RCC cells, and increased the expressions of MMP-13 and urokinase plasminogen activator (uPA). However, knockdown of PAR-2 by siRNA could intervene in all regulating effects of PAR-2AP. Furthermore, activation of PAR-2 induced the activation of PI3K and AKT, and PI3K/AKT inhibitor LY294002 attenuated the invasion and migration of RCC cells stimulated by PAR-2 activation. Altogether, our study demonstrates that PAR-2 stimulates the activation of PI3K/AKT pathway, subsequently increasing the expressions of MMP-13 and uPA, and thereby promotes the invasion and migration of RCC cells.
Copyright © 2015 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Invasion; MMP-13; PAR-2; PI3K/AKT pathway; Renal cell carcinoma; uPA

Mesh:

Substances:

Year:  2015        PMID: 25773677     DOI: 10.1016/j.yexmp.2015.03.018

Source DB:  PubMed          Journal:  Exp Mol Pathol        ISSN: 0014-4800            Impact factor:   3.362


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