Tumor Biology

, Volume 36, Issue 12, pp 9763–9767 | Cite as

The key role of astrocyte elevated gene-1 in CCR6-induced EMT in cervical cancer

  • Juan Zhang
  • Dingjun Zhu
  • Qiongying Lv
  • Yuexiong Yi
  • Fei Li
  • Wei Zhang
Research Article

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.

Keywords

AEG-1 CCR6 EMT Cervical cancer 

Notes

Acknowledgments

We greatly thank the other members of our lab for valuable suggestions and writing.

Conflicts of interest

None

References

  1. 1.
    Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001;37 Suppl 8:S4–66.CrossRefPubMedGoogle Scholar
  2. 2.
    Waggoner SE. Cervical cancer. Lancet. 2003;361:2217–25.CrossRefPubMedGoogle Scholar
  3. 3.
    Sheng X, Du X, Zhang X, et al. Clinical value of serum SPARC levels in early detection of recurrent squamous cell carcinoma of uterine cervix: comparison with serum SCCA, CYFRA21-1, and CEA levels. Croat Med J. 2009;50(5):455–64.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Rao Y, Wang H, Fan L, et al. Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/β-catenin complex. J Huazhong Univ Sci Technol Med Sci. 2011;31(1):1–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Shibata K, Kajiyama H, Ino K, et al. Twist expression in patients with cervical cancer is associated with poor disease outcome. Ann Oncol. 2008;19(1):81–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Su ZZ, Kang DC, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene. 2002;21:3592–602.CrossRefPubMedGoogle Scholar
  7. 7.
    Yoo BK, Emdad L, Su ZZ, et al. Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression. J Clin Invest. 2009;119:465–77.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee SG, Jeon HY, Su ZZ, et al. Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma. Oncogene. 2009;28:2476–84.CrossRefPubMedGoogle Scholar
  9. 9.
    Hu G, Chong RA, Yang Q, et al. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor prognosis breast cancer. Cancer Cell. 2009;15:9–20.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Liu K, Guo L, Miao L, et al. Ursolic acid inhibits epithelial–mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells. Anti-Cancer Drugs. 2013;24:494–503.CrossRefPubMedGoogle Scholar
  11. 11.
    Li J, Zhang N, Song LB, et al. Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Clin Cancer Res. 2008;14:3319–26.CrossRefPubMedGoogle Scholar
  12. 12.
    Weber CE, Li NY, Wai PY, et al. Epithelial-mesenchymal transition, TGF-β, and osteopontin in wound healing and tissue remodeling after injury. J Burn Care Res. 2012;33:311–8.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Soria G, Ben-Baruch A. The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett. 2008;267(2):271–85.CrossRefPubMedGoogle Scholar
  14. 14.
    Mencarelli A, Graziosi L, Renga B, et al. CCR5 antagonism by maraviroc reduces the potential for gastric cancer cell dissemination. Transl Oncol. 2013;6:784–93.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Sasaki S, Baba T, Shinagawa K, et al. Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice. Int J Cancer. 2014;135(6):1297–306.CrossRefPubMedGoogle Scholar
  16. 16.
    He W, He S, Wang Z, et al. Astrocyte elevated gene-1(AEG-1) induces epithelial-mesenchymal transition in lung cancer through activating Wnt/β-catenin signaling. BMC Cancer. 2015;15:1124.Google Scholar
  17. 17.
    Zheng J, Li C, Wu X, et al. Huaier polysaccharides suppresses hepatocarcinoma MHCC97-H cell metastasis via inactivation of EMT and AEG-1 pathway. Int J Biol Macromol. 2014;64:106–10.CrossRefPubMedGoogle Scholar
  18. 18.
    Khorramdelazad H, Mortazavi Y, Momeni M, et al. Lack of correlation between the CCR5-Δ32 mutation and acute myeloid leukemia in Iranian patients. Indian J Hematol Blood Transfus. 2015;31:29–31.CrossRefPubMedGoogle Scholar
  19. 19.
    Shi Y, Wu H, Zhang M, et al. Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol. 2013;8:89.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Shih JY, Yang PC. The EMT regulator slug and lung carcinogenesis. Carcinogenesis. 2011;32:1299–304.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Juan Zhang
    • 1
  • Dingjun Zhu
    • 1
  • Qiongying Lv
    • 1
  • Yuexiong Yi
    • 1
  • Fei Li
    • 1
  • Wei Zhang
    • 1
  1. 1.The First Department of GynaecologyRenmin Hospital of Wuhan UniversityWuhanChina

Personalised recommendations