ArticleBlood cancer journal2015
Lower expression of activating transcription factors 3 and 4 correlates with shorter progression-free survival in multiple myeloma patients receiving bortezomib plus dexamethasone therapy.
Article in Blood cancer journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis.Cancer research communications · 2024Article
- Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis.Acta pharmaceutica Sinica. B · 2024Article
- Factors determining the sensitivity to proteasome inhibitors of multiple myeloma cells.Frontiers in pharmacology · 2024Review
- The Prohibitin-Binding Compound Fluorizoline Activates the Integrated Stress Response through the eIF2α Kinase HRI.International journal of molecular sciences · 2023Article
- A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.Frontiers in molecular neuroscience · 2023Review
- Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma?Cancers · 2022Review
- Article
- Mitochondrial metabolic determinants of multiple myeloma growth, survival, and therapy efficacy.Frontiers in oncology · 2022Review
- Article
- Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer.Cancers · 2021Review
- Article
- The mevalonate pathway is an actionable vulnerability of t(4;14)-positive multiple myeloma.Leukemia · 2021Article
- Targeting the Integrated Stress Response in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.Journal of translational genetics and genomics · 2021Article
- Bortezomib Inhibits Multiple Myeloma Cells by Transactivating ATF3 to Trigger miR-135a-5p- Dependent Apoptosis.Frontiers in oncology · 2021Article
- Expression, mutation, and methylation of cereblon-pathway genes at pre- and post-lenalidomide treatment in multiple myeloma.Cancer science · 2020Article
- Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma.Scientific reports · 2020Article
- Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma.Experimental hematology & oncology · 2020Article
- Article
- Targeting the unfolded protein response in head and neck and oral cavity cancers.Experimental cell research · 2019Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bortezomib (BTZ), a proteasome inhibitor, is widely used in the treatment of multiple myeloma (MM), but a fraction of patients respond poorly to this agent. To identify factors predicting the duration of progression-free survival (PFS) of MM patients on BTZ treatment, the expression of proteasome and endoplasmic reticulum (ER) stress-related genes was quantified in primary samples from patients receiving a combination of BTZ and dexamethasone (BD). Fifty-six MM patients were stratified into a group with PFS<6 months (n=33) and a second group with PFS⩾6 months (n=23). Of the 15 genes analyzed, the expression of activating transcription factor 3 (ATF3) and ATF4 was significantly lower in patients with shorter PFS (P=0.0157 and P=0.0085, respectively). Chromatin immunoprecipitation analysis showed that these ATFs bind each other and transactivate genes encoding the pro-apoptotic transcription factors, CHOP and Noxa, which promote ER stress-associated apoptosis. When either ATF3 or ATF4 expression was silenced, MM cells partially lost sensitivity to BTZ treatment. This was accompanied by lower levels of Noxa, CHOP and DR5. Thus low basal expression of ATF3 and ATF4 may attenuate BTZ-induced apoptosis. Hence, ATF3 and ATF4 could potentially be used as biomarkers to predict efficacy of BD therapy in patients with MM.
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