1. HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion
- Author
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Pires, Isabel M, Blokland, Nina JG, Broos, Agnieke WT, Poujade, Flore-Anne, Senra, Joana M, Eccles, Suzanne A, Span, Paul N, Harvey, Amanda J, and Hammond, Ester M
- Abstract
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.
- Published
- 2014
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