The receptor tyrosine kinase Ax1 is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target

Deregulation of the receptor tyrosine kinase Ax1 has been implicated in the progression of several human cancers. However, the role of Ax1 in prostate cancer remains poorly understood, and the therapeutic efficacy of Ax1 targeting remains untested. In this report we identified Ax1 as a new therapeutic target for prostate cancer. Ax1 is consistently overexpressed in prostate cancer cell lines and human prostate tumors. Interestingly, the blockage of Ax1 gene expression strongly inhibits proliferation, migration, invasion and tumor growth. Furthermore, inhibition of Ax1 expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the nuclear factor-kappa B pathway. Additionally, blockage of Ax1 expression leads to inhibition of Akt, IKK alpha and I kappa B alpha phosphorylation, increasing I kappa B alpha expression and stability. Furthermore, induction of Akt phosphorylation by insulin-like growth factor 1 in Ax1 knockdown cells restores Akt activity and proliferation. Taken together, our results establish an unambiguous role for Ax1 in prostate cancer tumorigenesis with implications for prostate cancer treatment. Oncogene (2013) 32, 689-698; doi:10.1038/onc.2012.89; published online 12 March 2012