title: Protease-activated receptor 2 enhances renal cell carcinoma cell invasion and migration via PI3K/AKT signaling pathway.
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.
authors.affiliation: Department of Operating Theatre, Affiliated Hospital of Weifang Medical, University, Weifang, Shandong 261041, China.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Emergency Medicine, Affiliated Hospital of Weifang, Medical University, Weifang, Shandong 261041, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Surgery, Weifang Medical University, Weifang, Shandong 261053, China. Electronic address: jinshwu@163.com.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Wu
mesh_terms: D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D044464:Receptor, PAR-2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010960:Plasminogen Activators; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: Invasion; MMP-13; PAR-2; PI3K/AKT pathway; Renal cell carcinoma; uPA