ArticleClinical and experimental medicine2015
Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1.
Article in Clinical and experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- ER stress affects proliferation and induces polyploidization of cultured human HaCaT and A431 cells.Histochemistry and cell biology · 2026Article
- IFNγ-induced antigen loss in chimeric antigen receptor-T cell therapy.Frontiers in immunology · 2026Article
- Review
- Endothelial Unfolded Protein Response-Mediated Cytoskeletal Effects.Cell biochemistry and function · 2024Review
- Viral Infections and Their Ability to Modulate Endoplasmic Reticulum Stress Response Pathways.Viruses · 2024Review
- An epithelial cell-derived metabolite tunes immunoglobulin A secretion by gut-resident plasma cells.Nature immunology · 2023Article
- Review
- XBP1 impacts lung adenocarcinoma progression by promoting plasma cell adaptation to the tumor microenvironment.Frontiers in genetics · 2022Article
- eIF3k Domain-Containing Protein Regulates Conidiogenesis, Appressorium Turgor, Virulence, Stress Tolerance, and Physiological and Pathogenic Development ofFrontiers in plant science · 2021Article
- Deep Learning-Based Morphological Classification of Endoplasmic Reticulum Under Stress.Frontiers in cell and developmental biology · 2021Article
- Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties.The Journal of clinical investigation · 2020Article
- Nuclear factor-kappa B-dependent X-box binding protein 1 signalling promotes the proliferation of nucleus pulposus cells under tumour necrosis factor alpha stimulation.Cell proliferation · 2019Article
- Unravel the molecular mechanism of XBP1 in regulating the biology of cancer cells.Journal of Cancer · 2019Review
- Endoplasmic reticulum, Golgi, and lysosomes are disorganized in lung fibroblasts from chronic obstructive pulmonary disease patients.Physiological reports · 2018Article
- Deregulation of KSHV latency conformation by ER-stress and caspase-dependent RAD21-cleavage.PLoS pathogens · 2017Article
- Extracellular stress stimuli alter galectin expression profiles and adhesion characteristics of HL-60 cells.Molecular and cellular biochemistry · 2016Article
- An interdomain helix in IRE1α mediates the conformational change required for the sensor's activation.The Journal of biological chemistryArticle
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8 authors.
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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 more mature appearance with well-developed cytoplasm and a reduced nucleocytoplasmic ratio, and a further differentiated phenotype with markedly increased expression of CD49e together with significantly elevated cellular secretion of Ig light chain as shown by flow cytometry and ELISA, in contrast to the control myeloma cells without exposed to TM or DTT. Moreover, siRNA knockdown of XBP-1 disrupted TM- or DTT-induced myeloma cell differentiation and maturation. Our study, for the first time, validated that the modest activation of the UPR pathway enables myeloma cells to further differentiate, and identified that XBP-1 plays an indispensable role in UPR-mediated myeloma cell differentiation and maturation. Thus, we provided the rationale and feasibility for the exploration of the novel therapeutic strategy of differentiation induction for plasmacytic malignancies.
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