title: Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma.
abstract: In recent years, astrocyte elevated gene-1 (AEG-1) has been reported as a key mediator that is involved in the epithelial-to-mesenchymal transition (EMT) process. However, the mechanisms underlying CCL3/CCR5-AEG-1 pathway-mediated EMT in cardiac myxoma (CM) has not been well featured till now. We used immnohistochemistry and immunoblotting to assess the expression of CCR5 and AEG-1 in 30 cases of CM tissues and cells. Subsequently, cultured CM cells were treated with si-AEG-1 or si-CCR5 and then subjected to in vitro assays. We observed that CCR5 and AEG-1 proteins were highly expressed in CM tissues (73.3 and 76.7%, respectively) and closely correlated with tumor size (>5 cm). Importantly, we validated the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 increased in the CM cell with CCL3 treatment in a time- and concentration-dependent manner. When CM cells were treated with si-CCR5, the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was downregulated. In addition, when CM cells were treated with si-AEG-1, the expression of p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was also downregulated. Using the cell cycle and proliferation assay, the knockdown of AEG-1 inhibited the entry of G1 into S phase and the proliferation capacity of CM cells. In conclusion, AEG-1 mediates CCL3/CCR5-induced EMT development via both Erk1/2 and Akt signaling pathway in CM patients, which indicates CCL3/CCR5-AEG-1-EMT pathway could be suggested as a useful target to affect the progression of CM.
authors.affiliation: Department of Emergency Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Cardiosurgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Changcun
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Cardiosurgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Pang
mesh_terms: D000368:Aged; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D054405:Chemokine CCL3 / Q000008:administration & dosage / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006325:Heart Atria / Q000473:pathology; D006338:Heart Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009232:Myxoma / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D016601:RNA-Binding Proteins; D019713:Receptors, CCR5 / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C515429:CCL3 protein, human; C584933:CCR5 protein, human; D015815:Cell Adhesion Molecules; D054405:Chemokine CCL3; C483039:MTDH protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D019713:Receptors, CCR5; D051057:Proto-Oncogene Proteins c-akt