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Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo

Cancer Gene Therapy volume 20, pages 413–420 (2013)Cite this article

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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.

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Acknowledgements

We thank Dr Nicholas Denko, Stanford University School of Medicine, Stanford, CA, USA, for gifting cervical cancer cell lines. We also thank technical support by Mrs Rekha Rani, National Institute of Immunology, New Delhi, India, for confocal microscopy. This work is supported by grants from Indo-UK Cancer Research Program, Centre for Molecular Medicine, NII-core funding, Department of Biotechnology, Government of India.

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  1. S Agarwal: Author contributed equally to this work.

Authors and Affiliations

  1. Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India

    S Saini, S Agarwal, A Sinha, A Verma, D Parashar, N Gupta, N Jagadish & A Suri

  2. Department of Zoology, Centre for Advanced Studies, University of Rajasthan, Jaipur, India

    A S Ansari & N Kumar Lohiya

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  1. S Saini
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  2. S Agarwal
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Correspondence to A Suri.

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Saini, S., Agarwal, S., Sinha, A. et al. Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo. Cancer Gene Ther 20, 413–420 (2013). https://doi.org/10.1038/cgt.2013.32

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Keywords

  • cervical cancer
  • A-kinase anchor protein 4
  • gene silencing
  • migration and invasion.

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