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.
Written by:
Paccez JD, Vasques GJ, Correa RG, Vasconcellos JF, Duncan K, Gu X, Bhasin M, Libermann TA, Zerbini LF Are you the author?
International Center for Genetic Engineering and Biotechnology, Cancer Genomics Group, Cape Town, South Africa; Division of Medical Biochemistry, University of Cape Town, Cape Town, South Africa
Reference: Oncogene. 2012 Mar 12
doi: 10.1038/onc.2012.89
PubMed Abstract
PMID: 22410775