Oncotarget

Research Papers:

Mitochondrial protein 18 (MTP18) plays a pro-apoptotic role in chemotherapy-induced gastric cancer cell apoptosis

Lynn H.H. Aung, Ruibei Li, Bellur S. Prabhakar, Ajay V. Maker and Peifeng Li _

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Oncotarget. 2017; 8:56582-56597. https://doi.org/10.18632/oncotarget.17508

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Abstract

Lynn H.H. Aung1, Ruibei Li3, Bellur S. Prabhakar1, Ajay V. Maker1,2 and Peifeng Li1

1Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

2Division of Surgical Oncology, Department of Surgery, University of Illinois at Chicago, Creticos Cancer Center, Advocate Illinois Masonic Medical Center, Chicago, IL, USA

3School of Professional Studies, Northwestern University, Chicago, IL, USA

Correspondence to:

Peifeng Li, email: [email protected], [email protected]

Keywords: MTP18, mitochondrial fission, apoptosis, chemotherapy, gastric cancer

Received: February 13, 2017    Accepted: March 27, 2017    Published: April 28, 2017

ABSTRACT

One of the severe limitations of chemotherapy is the development of drug resistance. However, the mechanisms underlying chemotherapy resistance remain to be elucidated. Mitochondrial mediated apoptosis is a form of cell death induced by chemotherapy. Several chemotherapeutic agents have been shown to induce mitochondrial fission, and finally activate the apoptosis cascade in various cancer cells. Here, we report that the mitochondrial membrane protein 18 (MTP18) induced mitochondrial fragmentation in gastric cancer cells under doxorubicin (DOX) exposure. Upon over-expression of MTP18, a sub-cytotoxic dose of DOX could sensitize a significant number of cells to undergo mitochondrial fission and subsequent apoptosis. These findings suggest that MTP18 can enhance the sensitivity of gastric cancer cells to DOX. Mechanistically, we found that MTP18 enriched dynamic-related protein 1 (DRP1) accumulation in mitochondria and it was responsible for mediating DOX-induced signaling required for mitochondrial fission. Intriguingly, MTP18 expression was downregulated during DOX treatment. Thus, down-regulation of MTP18 expression could be one of the resistance factors interfering with DOX-induced apoptosis in gastric cancer cells.


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