RRC ID 52316
Author Yanoma T, Ogata K, Yokobori T, Ide M, Mochiki E, Toyomasu Y, Yanai M, Kogure N, Kimura A, Suzuki M, Nakazawa N, Bai T, Oyama T, Asao T, Shirabe K, Kuwano H.
Title Heat shock-induced HIKESHI protects cell viability via nuclear translocation of heat shock protein 70.
Journal Oncol Rep
Abstract 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.
Volume 38(3)
Pages 1500-1506
Published 2017-9-1
DOI 10.3892/or.2017.5844
PMID 28731175
MeSH Active Transport, Cell Nucleus / drug effects Active Transport, Cell Nucleus / genetics Aged Antineoplastic Agents / administration & dosage Antineoplastic Agents / adverse effects Carrier Proteins / genetics* Cell Line, Tumor Cell Nucleus / genetics Cell Proliferation / drug effects Cell Proliferation / genetics Cell Survival / drug effects Cell Survival / genetics Cytotoxins / administration & dosage Cytotoxins / adverse effects Female Gene Expression Regulation, Neoplastic / drug effects Gene Expression Regulation, Neoplastic / genetics* HSP70 Heat-Shock Proteins / genetics Heat-Shock Response / genetics* Humans Male Middle Aged RNA, Small Interfering / genetics Stomach Neoplasms / drug therapy Stomach Neoplasms / genetics* Stomach Neoplasms / pathology
IF 3.417
Times Cited 4
Human and Animal Cells MKN7(RCB0999) MKN74(RCB1002) MKN45(RCB1001) Kato III(RCB2088)