Journal Article

Heat shock-induced HIKESHI protects cell viability via nuclear translocation of heat shock protein 70

Kimura, Akiharu, Ide, Munenori, Yokobori, Takehiko, Bai, Tuya, Ogata, Kyoichi, Kogure, Norimichi, Mochiki, Erito, Toyomasu, Yoshitaka, Suzuki, Masaki, Asao, Takayuki, Oyama, Tetsunari, Kuwano, Hiroyuki, Yanoma, Toru, Yanai, Mitsuhiro, Nakazawa, Nobuhiro, Shirabe, Ken

2017

نظرة عامة

Heat shock proteins (HSPs), particularly HSP70, help restore normal cellular function following damage caused by stressors. HSP expression in tumor tissues indicates cancer progression, and while the development of HSP inhibitors is progressing, these substances are not widely used to treat cancer. HIKESHI (C11orf73) does not control the intracellular movement of HSP70 at normal temperatures; however, it does regulate the function and movements of HSP70 during heat shock. In this study, we examined the intracellular movement of HSP70 during heat shock to investigate the significance of HIKESHI expression in gastric cancer (GC) and determine if HIKESHI inhibition has cytotoxic effects. We examined HIKESHI using GC cell lines and immunostaining in 207 GC tissue samples. HIKESHI expression in GC tissues was associated with the progression of lymphatic invasion. Suppressing HIKESHI using siRNA did not affect cell viability at normal temperatures. However, suppressing HIKESHI during heat shock inhibited HSP70 nuclear transport and suppressed cell viability. Our results suggest that HIKESHI is a marker of cancer progression and that the combination of HIKESHI inhibition and hyperthermia is a therapeutic tool for refractory GC.

• الناشر: D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
• موضوع: Active Transport, Cell Nucleus - drug effects / Active Transport, Cell Nucleus - genetics / Aged / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - adverse effects / Binding sites / C11orf73 / cancer progression / Cancer therapies / Care and treatment / Carrier Proteins - genetics / Cell Line, Tumor / Cell Nucleus - genetics / Cell Proliferation - drug effects / Cell Proliferation - genetics / Cell Survival - drug effects / Cell Survival - genetics / Chemotherapy / Cytoplasm / Cytotoxins - administration & dosage / Cytotoxins - adverse effects / Development and progression / Female / Fever / Gastric cancer / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Gene Expression Regulation, Neoplastic - genetics / Genetic aspects / Health aspects / Heat / heat shock / Heat shock proteins / Heat-Shock Response - genetics / HIKESHI / HSP70 Heat-Shock Proteins - genetics / Humans / Male / Medical prognosis / Metastasis / Middle Aged / Proteins / RNA, Small Interfering - genetics / Stomach cancer / Stomach Neoplasms - drug therapy / Stomach Neoplasms - genetics / Stomach Neoplasms - pathology