Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.4161/cbt.29822

Type

Journal article

Journal

Cancer Biol Ther

Publication Date

10/2014

Volume

15

Pages

1350 - 1357

Keywords

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