Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1.

Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1. Clin Exp Med. 2013 Dec 20; Authors: Jiang H, Zou J, Zhang H, Fu W, Zeng T, Huang H, Zhou F, Hou J Abstract The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse differentiated phases, and the immaturity of myeloma cells has been taken as a marker for poor prognosis, suggesting that differentiation induction would be a promising therapeutic strategy for myeloma. Herein, we used low-dose pharmacological UPR inducers such as tunicamycin (TM) and dithiothreitol (DTT) to efficiently activate the IRE1-XBP-1 pathway in myeloma cells characterized by transcriptional expression increase in spliced XBP-1 and molecular chaperons, accompanied by significant differentiation and maturation of these myeloma cells, without concomitant cytotoxicity. These differentiated myeloma cells exhibited a...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: Clin Exp Med Source Type: research