HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

Poujade, Flore-Anne; Harvey, Amanda J.; Blokland, Nina J. G.; Broos, Agnieke W. T.; Eccles, Suzanne A.; Hammond, Ester M.; Pires, Isabel M.; Senra, Joana M.; Span, Paul N.

Abstract

© 2014 Landes Bioscience. 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.

Citation

Poujade, F.-A., Harvey, A. J., Blokland, N. J. G., Broos, A. W. T., Eccles, S. A., Hammond, E. M., Pires, I. M., Senra, J. M., & Span, P. N. (2014). HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion. Cancer Biology and Therapy, 15(10), 1350-1357. https://doi.org/10.4161/cbt.29822

• Acceptance Date: Jul 2, 2014
• Online Publication Date: Jul 14, 2014
• Publication Date: Oct 10, 2014
• Deposit Date: Apr 28, 2016
• Publicly Available Date: Apr 28, 2016
• Journal: Cancer biology and therapy
• Print ISSN: 1538-4047
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 10
• Pages: 1350-1357
• DOI: https://doi.org/10.4161/cbt.29822
• Keywords: PTK6, Brk, Hypoxia, Ubiquitylation, Migration, Invasion, Metastasis
• Public URL: https://hull-repository.worktribe.com/output/437356
• Publisher URL: http://www.tandfonline.com/doi/abs/10.4161/cbt.29822
• Additional Information: Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=kcbt20
• Contract Date: Apr 28, 2016