Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells

Kazuya Sumi, Kenji Tago, Tadashi Kasahara, Megumi Tago

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

JAK2 V617F mutant induces transformation through aberrant activation of various transcription factors. We found that the expression of Aurora kinase A (Aurka) was significantly induced by mutant JAK2 through c-Myc expression. Interestingly, mutant JAK2 enhanced resistance to cisplatin (CDDP)-induced DNA damage, and effectively suppressed apoptosis. Ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP, and this required kinase activity. Conversely, knockdown and inhibition of Aurka in cells expressing mutant JAK2 abolished the resistance to CDDP. Taken together, Aurka is most likely critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant.

Original languageEnglish
Pages (from-to)1884-1890
Number of pages7
JournalFEBS Letters
Volume585
Issue number12
DOIs
Publication statusPublished - 2011 Jun 23

Fingerprint

Aurora Kinase A
Cisplatin
Pharmaceutical Preparations
DNA Damage
Neoplasms
DNA
Transcription Factors
Phosphotransferases
Chemical activation
Cells
Apoptosis

Keywords

  • Aurora kinase A
  • Cisplatin
  • JAK2
  • Myeloproliferative neoplasm
  • V617F mutation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells. / Sumi, Kazuya; Tago, Kenji; Kasahara, Tadashi; Tago, Megumi.

In: FEBS Letters, Vol. 585, No. 12, 23.06.2011, p. 1884-1890.

Research output: Contribution to journalArticle

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