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: Juan Zhang, Dingjun Zhu, Qiongying Lv, Yuexiong Yi, Fei Li, Wei Zhang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 12 Pg. 9763-7 (Dec 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26156805 (Publication Type: Journal Article)

Chemical References

• CCL20 protein, human
• CCR6 protein, human
• Cell Adhesion Molecules
• Chemokine CCL20
• MTDH protein, human
• Membrane Proteins
• Neoplasm Proteins
• RNA-Binding Proteins
• Receptors, CCR6

Topics

• Adult
• Cell Adhesion Molecules (biosynthesis, genetics)
• Cell Line, Tumor
• Cell Proliferation
• Chemokine CCL20 (biosynthesis, genetics)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Membrane Proteins
• Middle Aged
• Neoplasm Proteins (biosynthesis)
• RNA-Binding Proteins
• Receptors, CCR6 (genetics)
• Signal Transduction
• Uterine Cervical Neoplasms (genetics, pathology)