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The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target

Oncogene volume 32, pages 689–698 (2013)Cite this article

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Abstract

Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers. However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested. In this report we identified Axl as a new therapeutic target for prostate cancer. Axl is consistently overexpressed in prostate cancer cell lines and human prostate tumors. Interestingly, the blockage of Axl gene expression strongly inhibits proliferation, migration, invasion and tumor growth. Furthermore, inhibition of Axl expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the nuclear factor-κB pathway. Additionally, blockage of Axl expression leads to inhibition of Akt, IKKα and IκBα phosphorylation, increasing IκBα expression and stability. Furthermore, induction of Akt phosphorylation by insulin-like growth factor 1 in Axl knockdown cells restores Akt activity and proliferation. Taken together, our results establish an unambiguous role for Axl in prostate cancer tumorigenesis with implications for prostate cancer treatment.

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Acknowledgements

JDP is recipient of the ICGEB post-doctoral fellowship. JFV is recipient of CAPES international fellowship. This study was supported by the Department of Defense grant PC051217 (LFZ), NIH grants 1RO1 CA85467 (TAL) and the Prostate Cancer Foundation (TAL).

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Author notes

  1. J D Paccez and G J Vasques: These two authors contributed equally to this work

Authors and Affiliations

  1. International Center for Genetic Engineering and Biotechnology, Cancer Genomics Group, Cape Town, South Africa

    J D Paccez, G J Vasques, K Duncan & L F Zerbini

  2. Division of Medical Biochemistry, University of Cape Town, Cape Town, South Africa

    J D Paccez & L F Zerbini

  3. Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

    R G Correa

  4. BIDMC Genomics and Proteomics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    J F Vasconcellos, X Gu, M Bhasin & T A Libermann

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  1. J D Paccez
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Correspondence to L F Zerbini.

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Paccez, J., Vasques, G., Correa, R. et al. The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target. Oncogene 32, 689–698 (2013). https://doi.org/10.1038/onc.2012.89

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