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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
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, No. 6, Year 2013
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Description
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, IKK and IκB phosphorylation, increasing IκB 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. © 2013 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Paccez, Juliano D.
South Africa, Cape Town
International Center for Genetic Engineering and Biotechnology
South Africa, Cape Town
University of Cape Town
Vasques, G. J.
South Africa, Cape Town
International Center for Genetic Engineering and Biotechnology
Corrêa, Ricardo Garcia
United States, San Diego
Sanford Burnham Prebys Medical Discovery Institute
Vasconcellos, J. F.
United States, Boston
Harvard Medical School
Duncan, Kristal C.
South Africa, Cape Town
International Center for Genetic Engineering and Biotechnology
Gu, Xuesong
United States, Boston
Harvard Medical School
Bhasin, Manoj K.
United States, Boston
Harvard Medical School
Libermann, Towia Aron
United States, Boston
Harvard Medical School
Zerbini, Luiz Fernando
South Africa, Cape Town
International Center for Genetic Engineering and Biotechnology
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 122
Authors: 9
Affiliations: 4
Identifiers
Doi:
10.1038/onc.2012.89
ISSN:
09509232
e-ISSN:
14765594
Research Areas
Cancer
Genetics And Genomics