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Research Papers:

Nuclear heat shock protein 110 expression is associated with poor prognosis and chemotherapy resistance in gastric cancer

Akiharu Kimura, Kyoichi Ogata, Bolag Altan, Takehiko Yokobori, Munenori Ide, Erito Mochiki, Yoshitaka Toyomasu, Norimichi Kogure, Toru Yanoma, Masaki Suzuki, Tuya Bai, Tetsunari Oyama and Hiroyuki Kuwano _

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Oncotarget. 2016; 7:18415-18423. https://doi.org/10.18632/oncotarget.7821

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Abstract

Akiharu Kimura1, Kyoichi Ogata1, Bolag Altan1, Takehiko Yokobori1, Munenori Ide2, Erito Mochiki3, Yoshitaka Toyomasu1, Norimichi Kogure1, Toru Yanoma1, Masaki Suzuki1, Tuya Bai1, Tetsunari Oyama2, Hiroyuki Kuwano1

1Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

2Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

3Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Correspondence to:

Hiroyuki Kuwano, e-mail: hkuwano@gunma-u.ac.jp

Keywords: cancer progression, drug resistance, gastric cancer, heat shock protein, heat shock protein 110

Received: September 25, 2015     Accepted: January 23, 2016     Published: March 01, 2016

ABSTRACT

Heat shock protein (HSP) expression is induced by the exposure to stress, such as fever, oxidative stress, chemical exposure, and irradiation. In cancer, HSP promotes the survival of malignant cells by inhibiting the induction of apoptosis. In colorectal cancer, a loss-of-function mutation of HSP110 (HSP110ΔE9) has been identified. HSP110ΔE9 inhibits the nuclear translocation of wild-type HSP110, which is important for its chaperone activity and anti-apoptotic effects. The patients carrying HSP110ΔE9 mutation exhibit high sensitivity to anticancer agents, such as oxaliplatin and 5-fluorouracil. There is still insufficient information about HSP110 localization, the clinicopathological significance of HSP110 expression, and its association with chemotherapy resistance in gastric cancer. Here, we found that high nuclear expression of HSP110 in gastric cancer tissues is associated with cancer progression, poor prognosis, and recurrence after adjuvant chemotherapy. In vitro results showed that HSP110 suppression increases the sensitivity to 5-fluorouracil and cisplatin of human gastric cancer cell lines. Our results suggest that nuclear HSP110 may be a new drug sensitivity marker for gastric cancer and a potential molecular therapeutic target for the treatment of gastric cancer patients with acquired anticancer drug resistance.


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