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Context‐specific protein tyrosine kinase 6 ( PTK 6) signalling in prostate cancer
Author(s) -
Zheng Yu,
Tyner Angela L.
Publication year - 2013
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12050
Subject(s) - cancer research , protein kinase b , tyrosine kinase , lncap , biology , prostate cancer , proto oncogene tyrosine protein kinase src , anoikis , kinase , tyrosine phosphorylation , focal adhesion , signal transduction , microbiology and biotechnology , cancer cell , cancer , genetics
Background Protein tyrosine kinase 6 ( PTK 6) is an intracellular tyrosine kinase that is distantly related to SRC family kinases. PTK 6 is nuclear in normal prostate epithelia, but nuclear localization is lost in prostate tumours. Increased expression of PTK 6 is detected in human prostate cancer, especially at metastatic stages, and in other types of cancers, including breast, colon, head and neck cancers, and serous carcinoma of the ovary. Materials and methods Potential novel substrates of PTK 6 identified by mass spectrometry were validated in vitro . The significance of PTK 6‐induced phosphorylation of these substrates was addressed using human prostate cell lines by knockdown of endogenous PTK 6 or overexpression of targeted PTK 6 to different intracellular compartments. Results We identified AKT , p130 CAS and focal adhesion kinase ( FAK ) as novel PTK 6 substrates and demonstrated their roles in promoting cell proliferation, migration and resistance to anoikis. In prostate cancer cells, active PTK 6 is primarily associated with membrane compartments, although the majority of total PTK 6 is localized within the cytoplasm. Ectopic expression of membrane‐targeted PTK 6 transforms immortalized fibroblasts. Knockdown of endogenous cytoplasmic PTK 6 in PC 3 prostate cancer cells impairs proliferation, migration and anoikis resistance. However, re‐introduction of PTK 6 into the nucleus significantly decreases cell proliferation, suggesting context‐specific functions for nuclear PTK 6. Conclusions In human prostate cancer, elevated PTK 6 expression, translocation of PTK 6 from the nucleus to the cytoplasm and its activation at the plasma membrane contribute to increased phosphorylation and activation of its substrates such as AKT , p130 CAS and FAK , thereby promoting prostate cancer progression.