Research Article Epigenetic Silencing of CXCR4 Promotes Loss of Cell Adhesion in Cervical Cancer Suresh Singh Yadav, 1 Shyam Babu Prasad, 1 Mitali Das, 1 Soni Kumari, 1 Lakshmi Kant Pandey, 2 Sunita Singh, 3 Satyajit Pradhan, 4 and Gopeshwar Narayan 1 1 Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India 2 Department of Obstetrics and Gynecology, Banaras Hindu University, Varanasi 221005, India 3 Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi 221005, India 4 Department of Radiotherapy & Radiation Medicine, Banaras Hindu University, Varanasi 221005, India Correspondence should be addressed to Gopeshwar Narayan; gnarayan@bhu.ac.in 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. Tis 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. In the network of chemokine signaling pathways, recent reports have described the SDF-1/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- 1 promotes the loss of cell adhesion while paracrine SDF-1 predominantly protects the normal cervical cells from loss of cell adhesion. Cervical cancer cell line C-33A having increased expression of CXCR4 afer TSA treatment showed increased cell adhesion by paracrine source of SDF-1 in comparison to untreated C-33A. Tese fndings demonstrate the frst evidence that epigenetic silencing of CXCR4 makes the cells inefcient to respond to the paracrine source of SDF-1 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- 1/CXCR4 signaling in tumor microenvironment which may be promising to further delineate molecular mechanism of cervical carcinogenesis. 1. Introduction Te process of cancer progression and metastasis, driven by chemokines and its receptors, is a major cause of death in cancer patients [1, 2]. Chemokines are a family of chemoat- tractive cytokines and are grouped into C, CC, CXC, and CX3C subfamilies based on the position of conserved cys- teine residues [3, 4]. Chemokine receptors are a family of seven transmembrane G protein-coupled cell surface recep- tors (GPCRs) and are defned by their ability to induce direc- tional migration of cells towards a gradient of chemokine (chemotaxis). Tese receptors, initially identifed on leu- kocytes, are present on many diferent cell types. It has been demonstrated that hematopoietic and nonhematopoietic cells express these receptors for various chemokines that are constitutively expressed in tumor microenvironments [5]. Te cross talk between cancer cells and their microenvi- ronment has an important infuence on tissue homeostasis and progression of cancers [6]. Chemokines are the major mediators of this cross talk between tumor cell and stroma [7]. Te interactions between chemokine receptors and their respective chemokines help to coordinate the tumor cell growth and trafcking [8]. Among chemokine signaling axes, the SDF-1/CXCR4 has been demonstrated to have a critical role in various solid tumors [9]. CXCR4 is a G protein-coupled transmembrane receptor initially identifed as a cofactor for HIV entry into CD4 + T cells [10]. Activation of CXCR4 with SDF-1 triggers G protein signaling that activates a variety of intracellu- lar signal transduction pathways and molecules regulating Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 581403, 13 pages http://dx.doi.org/10.1155/2014/581403