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

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.