title: The key role of astrocyte elevated gene-1 in CCR6-induced EMT in cervical cancer.
abstract: In recent years, astrocyte elevated gene-1 (AEG-1) has been recommended as an important mediator that is involved in the epithelial-to-mesenchymal transition (EMT) process. However, the mechanisms underlying the chemokine (C-C motif) ligand 20 (CCL20)/chemokine (C-C motif) receptor 6 (CCR6)-AEG-1 pathway-mediated EMT in cervical cancer (CC) have not been well featured till now. We used immunohistochemistry and immunoblotting to assess the expression of AEG-1 in 94 cervical cancer tissues and cells. Subsequently, cervical cancer SiHa cells were treated with si-AEG-1 and then subjected to in vitro assays. We observed that AEG-1 proteins were highly expressed in cervical cancer tissues and closely correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and metastasis. Importantly, we validated the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin, and matrix metalloproteinase 2 (MMP2) increased in SiHa with CCL20 treatment in a concentration-dependent manner. When 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 assay, the knockdown of AEG-1 inhibited the entry of G1 into S phase. In conclusion, AEG-1 mediates CCL20/CCR6-induced EMT development via both Erk1/2 and Akt signaling pathway in cervical cancer, which indicates that CCL20/CCR6-AEG-1-EMT pathway could be suggested as a useful target to affect the progression of cervical cancer.
authors.affiliation: The First Department of Gynaecology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The First Department of Gynaecology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China.
authors.forename: Dingjun
authors.initials: D
authors.lastname: Zhu
authors.affiliation: The First Department of Gynaecology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China.
authors.forename: Qiongying
authors.initials: Q
authors.lastname: Lv
authors.affiliation: The First Department of Gynaecology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China.
authors.forename: Yuexiong
authors.initials: Y
authors.lastname: Yi
authors.affiliation: The First Department of Gynaecology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: The First Department of Gynaecology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, China. zhangjuanwh163@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054418:Chemokine CCL20 / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D054399:Receptors, CCR6 / Q000235:genetics*; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D015815:Cell Adhesion Molecules; D054418:Chemokine CCL20; C483039:MTDH protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D054399:Receptors, CCR6
keywords: AEG-1; CCR6; Cervical cancer; EMT