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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

Flore-Anne Poujade

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., Harvey, A. J., Blokland, N. J. G., Broos, A. W. T., Eccles, S. A., Hammond, E. 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 Mar 29, 2024
Journal Cancer biology and therapy
Print ISSN 1538-4047
Electronic ISSN 1555-8576
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