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Title 

Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer

Authors 

Tae Woo KimSeon-Jin LeeYoung-Jun ParkSang Yoon ParkByung Moo OhYun Sun ParkBo Yeon KimY H LeeHee Jun ChoSuk Ran YoonYong Kyung ChoeHee Gu Lee

Publisher 

Springer Verlag (Germany)

Issue Date 

2017

Citation 

Tumor Biology

Keywords 

cell deathdocetaxelmitochondrial depolarizationmitophagyOpa-interacting protein 5

Abstract 

Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer. The activation of mitophagy by Neisseria gonorrhoeae opacity-associated-interacting protein 5 overexpression promoted cell survival, preventing docetaxel-induced mitochondrial clearance. Conversely, short interfering RNA?mediated knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 accelerated docetaxel-induced apoptosis while increasing mitochondrial depolarization, reactive oxygen species, and endoplasmic reticulum stress and decreasing adenosine triphosphate production. We also found that the mitochondrial outer membrane proteins mitofusin 2 and phosphatase and tensin homolog?induced putative kinase 1 colocalized with Neisseria gonorrhoeae opacity-associated-interacting protein 5 in mitochondria and that mitofusin 2 knockdown altered Neisseria gonorrhoeae opacity-associated-interacting protein 5 expression. These findings indicate that Neisseria gonorrhoeae opacity-associated-interacting protein 5 modulates docetaxel-induced mitophagic cell death and therefore suggest that this protein comprises a potential therapeutic target for gastric cancer treatment

ISSN 

1010-4283

Link 

http://dx.doi.org/10.1177/1010428317733985

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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