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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

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.

Publication Date Oct 10, 2014
Journal Cancer biology and therapy
Print ISSN 1538-4047
Electronic ISSN 1555-8576
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Volume 15
Issue 10
Pages 1350-1357
Institution 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
DOI https://doi.org/10.4161/cbt.29822
Keywords PTK6, Brk, Hypoxia, Ubiquitylation, Migration, Invasion, Metastasis
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....cope&journalCode=kcbt20

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