The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

Orit Uziel, Gil Kanfer, Einat Beery, Dana Yelin, Daniel Shepshelovich, Mary Bakhanashvili, Jardena Nordenberg, Meir Lahav

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number1
DOIs
StatePublished - 18 Jul 2014
Externally publishedYes

Keywords

  • Erythropoietin
  • Lyn-src
  • Telomerase
  • Telomeres

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