title: C5a receptor enhances hepatocellular carcinoma cell invasiveness via activating ERK1/2-mediated epithelial-mesenchymal transition.
abstract: C5a and its receptor, C5a receptor (C5aR), play critical roles in tumor progression. However, mechanisms of C5a-C5aR axis in hepatocellular carcinoma (HCC) cell invasiveness are not fully elucidated. In this study, we found that C5aR expression was highly expressed in HCC cell lines and tumor tissues, and associated with capsular invasion, tumor stage and some epithelial-mesenchymal transition (EMT)-related markers. Activation of C5aR by C5a promoted HCC cell invasion and migration, whereas depletion of C5aR expression significantly impaired C5a-stimulated invasion and migration. Furthermore, we found that C5aR induced EMT in HCC cells, through downregulation of E-cadherin and Claudin-1 expression, and upregulation of Snail expression. Finally, we demonstrated that C5aR stimulated activation of ERK1/2, and ERK1/2 pathway was involved in C5aR-mediated EMT, cell invasion and migration of HCC cells. Thus, our data suggest that C5aR stimulates cell invasion and migration via ERK1/2-mediated EMT in HCC cells, and implicate that blocking C5aR expression has therapeutic promise to inhibit HCC invasiveness.
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejing, China.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Hu
authors.affiliation: Department of Interventional Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejing, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejing, China.
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Dong
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejing, China.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Zhou
authors.affiliation: Department of Interventional Radiology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejing, China. Electronic address: xxiangyu1@163.com.
authors.forename: Xi-Xiang
authors.initials: XX
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics* / Q000378:metabolism
chemical_list: C488033:C5AR1 protein, human; D015820:Cadherins; D044087:Receptor, Anaphylatoxin C5a
keywords: C5a receptor; ERK1/2; Epithelial–mesenchymal transition; Hepatocellular carcinoma; Invasion; Migration