Pires, I. M., Blokland, N. J. G., Broos, A. W. T., Poujade, F. A., Senra, J. M., Eccles, S. A., Span, P. N., Harvey, A. J., Hammond, E. M. (2014) HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion. Cancer Biology & Therapy, 15 (10). pp. 1350-1357. ISSN 1538-4047

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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.

Item Type:	Article
Authors (ICR Faculty only):	Eccles, Sue
All Authors:	Pires, I. M., Blokland, N. J. G., Broos, A. W. T., Poujade, F. A., Senra, J. M., Eccles, S. A., Span, P. N., Harvey, A. J., Hammond, E. M.
Additional Information:	ISI Document Delivery No.: AZ7EL Times Cited: 0 Cited Reference Count: 43 Pires, Isabel M. Blokland, Nina J. G. Broos, Agnieke W. T. Poujade, Flore-Anne Senra, Joana M. Eccles, Suzanne A. Span, Paul N. Harvey, Amanda J. Hammond, Ester M. Breast Cancer Campaign pilot grant; University of Hull; Royal Society; Breast Cancer Campaign pilot grants; ICR HEFCE; Cancer Research UK [C309/A11566]; Brunel University; Cancer Research UK We would like to thank Dr Anderson Ryan, Dr Jason Parsons, Dr Stephen Maher, and Professor John Greenman for useful discussions. A Breast Cancer Campaign pilot grant awarded to E.M.H. supported this study. I.M.P. is supported by University of Hull HEFCE funding, and Royal Society and Breast Cancer Campaign pilot grants. S.A.E. is supported by ICR HEFCE funding and Cancer Research UK program grant C309/A11566. A.H. is supported by Brunel University HEFCE funding. E.M.H. is supported by a Cancer Research UK grant. Taylor & francis inc Philadelphia
Uncontrolled Keywords:	PTK6 Brk hypoxia ubiquitylation migration invasion metastasis protein-tyrosine kinase breast-cancer cells epidermal-growth-factor prostate tumor-cells inducible factors epithelial-cells brk activation physiology expression
Research teams:	ICR divisions > Cancer Therapeutics > Tumour Biology & Metastasis
Depositing User:	Alexander Smithson
Date Deposited:	23 Feb 2015 16:28
Last Modified:	23 Feb 2015 16:28
URI:	http://publications.icr.ac.uk/id/eprint/13914

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