More than 25 years have passed since the discovery of protein tyrosine kinase 6 (PTK6), a non-receptor tyrosine kinase distantly related to SRC family kinases. Since then, a variety of data suggest that PTK6 promotes oncogenic signaling and tumorigenesis, generally dependent on its kinase activity. Increased PTK6 expression, activation at the plasma membrane and altered intracellular localization have been discovered in prostate cancers. While PTK6 is localized to nuclei of epithelial cells in normal prostate, it is relocalized and activated at the plasma membrane in prostate tumors. Active PTK6 interacts with and directly phosphorylates AKT, FAK and BCAR1 to promote oncogenic signaling. Furthermore, PTK6 can enhance the epithelial mesenchymal transition by inhibiting E-cadherin expression and inducing expression of the mesenchymal markers vimentin, SLUG and ZEB1. Several lines of evidence suggest that PTK6 plays a role in Pten null prostate tumors. PTEN targets activating phosphorylation of PTK6 and loss of PTEN subsequently leads to PTK6 activation. Different studies provide compelling evidence as to why PTK6 is a potential therapeutic target in prostate cancer. Here, we briefly review the advances and significance of PTK6 in prostate cancer.
Keywords: BRK; PTEN; PTK6; prostate cancer; tyrosine kinase.
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