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 Funakoshi-Tago

doi:10.1016/j.febslet.2011.04.068

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 Funakoshi-Tago

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

33 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 language	English
Pages (from-to)	1884-1890
Number of pages	7
Journal	FEBS Letters
Volume	585
Issue number	12
DOIs	https://doi.org/10.1016/j.febslet.2011.04.068
Publication status	Published - 2011 Jun 23

Keywords

Aurora kinase A
Cisplatin
JAK2
Myeloproliferative neoplasm
V617F mutation

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.febslet.2011.04.068

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title = "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.",

keywords = "Aurora kinase A, Cisplatin, JAK2, Myeloproliferative neoplasm, V617F mutation",

author = "Kazuya Sumi and Kenji Tago and Tadashi Kasahara and Megumi Funakoshi-Tago",

note = "Funding Information: We thank Dr. J.N. Ihle for the retroviral vectors of JAK2 and EpoR. This work was supported in part by grants ( 21790090 ) from MEXT and Takeda Science Foundation . ",

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T1 - Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells

AU - Sumi, Kazuya

AU - Tago, Kenji

AU - Kasahara, Tadashi

AU - Funakoshi-Tago, Megumi

N1 - Funding Information: We thank Dr. J.N. Ihle for the retroviral vectors of JAK2 and EpoR. This work was supported in part by grants ( 21790090 ) from MEXT and Takeda Science Foundation .

PY - 2011/6/23

Y1 - 2011/6/23

N2 - 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.

AB - 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.

KW - Aurora kinase A

KW - Cisplatin

KW - JAK2

KW - Myeloproliferative neoplasm

KW - V617F mutation

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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