Oncotarget

Research Papers:

Phosphorylation of caspase-9 at Thr125 directs paclitaxel resistance in ovarian cancer

Mi Ran Byun and Jin Woo Choi _

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Oncotarget. 2018; 9:1041-1047. https://doi.org/10.18632/oncotarget.23133

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Abstract

Mi Ran Byun1 and Jin Woo Choi1

1Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea

Correspondence to:

Jin Woo Choi, email: [email protected]

Keywords: ovarian cancer; paclitaxel-induced resistance; caspase-9; CDK1

Received: August 21, 2017     Accepted: November 17, 2017     Published: December 08, 2017

ABSTRACT

Although paclitaxel is routinely prescribed for the treatment of epithelial ovarian cancer (EOC), paclitaxel resistance is common in EOC and correlates with short survival of patients. A previous pharmacogenomic study revealed the importance of cyclin-dependent kinase 1 (CDK1) activity in drug response. However, a subsequent research showed that the expression level of CDK1 failed to show significant correlation with delayed apoptosis and patient survival. On the contrary, the expression and phosphorylation of capase-9, the downstream target molecule of CDK1, appeared to determine drug resistance. Our results suggest that treatment with the CDK1 inhibitor alsterpaullone reduces phosphorylation of caspase-9. Moreover, caspase-9 phosphorylation was dependent on CDK1 activity and phospho-caspase-9 level directs paclitaxel resistance. This observation was reproducible in xenografted tumors. Thus, the regulation of caspase-9 may be a novel therapeutic strategy to reverse paclitaxel-induced resistance in ovarian cancer cells.


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