title: HDAC Inhibitors and RECK Modulate Endoplasmic Reticulum Stress in Tumor Cells.
abstract: In the tumor microenvironment hypoxia and nutrient deprived states can induce endoplasmic reticulum (ER) stress. If ER stress is not relieved, the tumor cells may become apoptotic. Therefore, targeting ER homeostasis is a potential strategy for cancer treatment. Various chemotherapeutic agents including histone deacetylase (HDAC) inhibitors can induce ER stress to cause cell death in cancers. Some HDAC inhibitors can prevent HDAC from binding to the specificity protein 1-binding site of the promoter of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and up-regulate RECK expression. Up-regulation of RECK expression by HDAC inhibitors has been observed in various cancer types.RECKis a tumor and metastasis suppressor gene and is critical for regulating tumor cell invasiveness and metastasis. RECK also modulates ER stress via binding to and sequestering glucose-regulated protein 78 protein, so that the transmembrane sensors, such as protein kinase RNA-like ER kinase are released to activate eukaryotic translational initiation factor 2α phosphorylation and enhance ER stress. Therefore, HDAC inhibitors may directly induce ER stress or indirectly induce this stress by up-regulating RECK in cancer cells.
authors.affiliation: Department of Surgery, Far Eastern Memorial Hospital, 21, Sec. 2, Nan-Ya South Road, Banciao, Taipei 220, Taiwan. ychen@mail.femh.org.tw.|Department of Chemical Engineering and Materials Science, Yuan Ze University, 135 Yuan Tung Rd., Chung-Li, Taoyuan 320, Taiwan. ychen@mail.femh.org.tw.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgery, Far Eastern Memorial Hospital, 21, Sec. 2, Nan-Ya South Road, Banciao, Taipei 220, Taiwan. yahuitsai@gmail.com.|Department of Chemical Engineering and Materials Science, Yuan Ze University, 135 Yuan Tung Rd., Chung-Li, Taoyuan 320, Taiwan. yahuitsai@gmail.com.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan S. Rd., Taipei 100, Taiwan. tsh5110@ntu.edu.tw.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Tseng
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D058851:GPI-Linked Proteins / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D058851:GPI-Linked Proteins; D056572:Histone Deacetylase Inhibitors
keywords: cancers; endoplasmic reticulum stress; histone deacetylase inhibitors; reversion-inducing cysteine-rich protein with Kazal motifs