HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion.

IM Pires, NJ Blokland, AW Broos, FA Poujade, JM Senra, SA Eccles, PN Span, AJ Harvey, EM Hammond

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1350-1357
Number of pages8
JournalCancer Biology and Therapy
Volume15
Issue number10
Early online date14 Jul 2014
DOIs
Publication statusPublished - Oct 2014

Keywords

  • PTK6
  • Brk
  • hypoxia
  • ubiquitylation
  • migration
  • invasion
  • metastasis

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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