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Title: HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion
Authors: Pires, IM
Blokland, NJG
Broos, AWT
Poujade, F-A
Senra, JM
Eccles, SA
Span, PN
Harvey, AJ
Hammond, EM
Keywords: Brk;Hypoxia;Invasion;Metastasis;Migration;PTK6;Ubiquitylation
Issue Date: 2014
Publisher: Landes Bioscience
Citation: Cancer Biology and Therapy, 2014, 15 (10), pp. 1350 - 1357
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.
Description: This article has been made available through the Brunel Open Access Publishing Fund.
ISSN: 1538-4047
Appears in Collections:Brunel OA Publishing Fund
Dept of Life Sciences Research Papers

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