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BioMed Research International
Volume 2014, Article ID 581403, 13 pages
http://dx.doi.org/10.1155/2014/581403
Research Article

Epigenetic Silencing of CXCR4 Promotes Loss of Cell Adhesion in Cervical Cancer

1Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India
2Department of Obstetrics and Gynecology, Banaras Hindu University, Varanasi 221005, India
3Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi 221005, India
4Department of Radiotherapy & Radiation Medicine, Banaras Hindu University, Varanasi 221005, India

Received 24 February 2014; Revised 31 May 2014; Accepted 31 May 2014; Published 10 July 2014

Academic Editor: Jozef Zustin

Copyright © 2014 Suresh Singh Yadav et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In the network of chemokine signaling pathways, recent reports have described the SDF-1α/CXCR4 axis and its role in cancer progression and metastasis. Interestingly, we found downregulation of CXCR4 at both transcript and protein level in cervical cancer cell lines and primary tumors. We also found CXCR4 promoter hypermethylation in cervical cancer cell lines and primary biopsy samples. DNA hypomethylating drug 5-AZA-2′-deoxycytidine and histone deacetylase inhibitor Trichostatin A treatments in cell lines reactivate both CXCR4 transcription and protein expression. Cell adhesion assay demonstrated that autocrine SDF-1α promotes the loss of cell adhesion while paracrine SDF-1α predominantly protects the normal cervical cells from loss of cell adhesion. Cervical cancer cell line C-33A having increased expression of CXCR4 after TSA treatment showed increased cell adhesion by paracrine source of SDF-1α in comparison to untreated C-33A. These findings demonstrate the first evidence that epigenetic silencing of CXCR4 makes the cells inefficient to respond to the paracrine source of SDF-1α leading to loss of cell adhesion, one of the key events in metastases and progression of the disease. Our results provide novel insight of SDF-1α/CXCR4 signaling in tumor microenvironment which may be promising to further delineate molecular mechanism of cervical carcinogenesis.