Flore-Anne Poujade
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.
Authors
Amanda J. Harvey
Nina J. G. Blokland
Agnieke W. T. Broos
Suzanne A. Eccles
Ester M. Hammond
Isabel M. Pires
Joana M. Senra
Paul N. Span
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 |
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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 |
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Copyright Statement
©2014 The authors
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