title: Nuclear heat shock protein 110 expression is associated with poor prognosis and chemotherapy resistance in gastric cancer.
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.
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Akiharu
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ogata
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Bolag
authors.initials: B
authors.lastname: Altan
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Munenori
authors.initials: M
authors.lastname: Ide
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
authors.forename: Erito
authors.initials: E
authors.lastname: Mochiki
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Toyomasu
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Kogure
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yanoma
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tuya
authors.initials: T
authors.lastname: Bai
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D050957:HSP110 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
chemical_list: D050957:HSP110 Heat-Shock Proteins
keywords: cancer progression; drug resistance; gastric cancer; heat shock protein; heat shock protein 110