title: Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo.
abstract: Earlier, we reported an association of A-kinase anchor protein 4 (AKAP4) expression in cervical cancer patient specimens, indicating its implications as an immunotherapeutic target. In this study, we investigated the possible role of AKAP4 in cervical carcinogenesis. AKAP4 messenger RNA and protein expression was assessed in four cervical cancer cell line models, C-33A, CaSki, HeLa and SiHa. Gene silencing approach was employed to investigate the potential role of AKAP4 in cellular growth, proliferation, colony-forming ability, migration and invasion in aggressive squamous cell carcinoma cells (SiHa). Further, the effect of downregulation of AKAP4 on tumor growth was examined in the cervical cancer xenograft model in nude mice. Our data clearly indicated that AKAP4 was expressed in all cervical cancer cells at the gene and protein level. We also observed distinct cytoplasmic and surface localization by indirect immunofluorescence and flow cytometry, respectively. Ablation of AKAP4 protein caused significant inhibition in cellular proliferation, colony-forming ability, migration and invasion ability of SiHa cells. Further, gene silencing of AKAP4 also resulted in reduced tumor growth in nude mice in vivo. Collectively, AKAP4 surface localization and its significant association with malignant properties of cervical cancer cells imply its clinical utility as an immunotherapeutic target.
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Saini
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
authors.forename: A
authors.initials: A
authors.lastname: Sinha
authors.forename: A
authors.initials: A
authors.lastname: Verma
authors.forename: D
authors.initials: D
authors.lastname: Parashar
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.forename: A S
authors.initials: AS
authors.lastname: Ansari
authors.forename: N Kumar
authors.initials: NK
authors.lastname: Lohiya
authors.forename: N
authors.initials: N
authors.lastname: Jagadish
authors.forename: A
authors.initials: A
authors.lastname: Suri
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D054758:A Kinase Anchor Proteins; C485480:AKAP4 protein, human; D034741:RNA, Small Interfering