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PTK6/Brk is a non-receptor tyrosine kinase overexpressed in cancer. Here we demonstrate that cytosolic PTK6 is rapidly and robustly induced in response to hypoxic conditions in a HIF-1-independent manner. Furthermore, a proportion of hypoxic PTK6 subsequently re-localized to the cell membrane. We observed that the rapid stabilization of PTK6 is associated with a decrease in PTK6 ubiquitylation and we have identified c-Cbl as a putative PTK6 E3 ligase in normoxia. The consequences of hypoxia-induced PTK6 stabilization and subcellular re-localization to the plasma membrane include increased cell motility and invasion, suggesting PTK6 targeting as a therapeutic approach to reduce hypoxia-regulated metastatic potential. This could have particular significance for breast cancer patients with triple negative disease.

Original publication




Journal article


Cancer Biol Ther

Publication Date





1350 - 1357


Brk, PTK6, hypoxia, invasion, metastasis, migration, ubiquitylation, Cell Hypoxia, Cell Line, Tumor, Cell Movement, Colorectal Neoplasms, Disease-Free Survival, Female, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Proteins, Oxygen, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-cbl, Triple Negative Breast Neoplasms, Ubiquitination