ArticleOncotarget2015
KLF4-SQSTM1/p62-associated prosurvival autophagy contributes to carfilzomib resistance in multiple myeloma models.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.Cell death & disease · 2026Article
- Survival Genie 2: a next-generation web server for targeted and single-cell-based survival analyses.Genome medicine · 2026Article
- RVd and CyBorD therapies remodel B-cell maturation signaling and alter immune and clonal architecture in multiple myeloma.Cancer biology & therapy · 2025Article
- The role and mechanism of transcription factor KLF4 in regulating mitochondrial damage and apoptosis by activating chondrocyte autophagy in osteoarthritis.Scientific reports · 2025Article
- Canagliflozin differentially modulates carfilzomib-induced endoplasmic reticulum stress in multiple myeloma and endothelial cells.Archives of toxicology · 2025Article
- Mechanism of Drug Resistance to First-Line Chemotherapeutics Mediated by TXNDC17 in Neuroblastomas.Cancer reports (Hoboken, N.J.) · 2024Article
- B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.Blood cancer journal · 2024Article
- KLF4 targets RAB26 and decreases 5-FU resistance through inhibiting autophagy in colon cancer.Cancer biology & therapy · 2023Article
- Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2023Review
- Autophagy-related mechanisms for treatment of multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Kruppel-like factor 2 contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by augmenting autophagic flux.Theranostics · 2023Article
- Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma.Nature communications · 2022Article
- Geranylgeranyl diphosphate synthase inhibitor and proteasome inhibitor combination therapy in multiple myeloma.Experimental hematology & oncology · 2022Article
- Contribution of the Tumor Microenvironment to Metabolic Changes Triggering Resistance of Multiple Myeloma to Proteasome Inhibitors.Frontiers in oncology · 2022Review
- Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).International journal of oncology · 2021Review
- Research progress in proteasome inhibitor resistance to multiple myeloma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Article
- Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 (KLF4) was identified as a contributing factor. Expression levels as well as nuclear localization of KLF4 protein were elevated in MM cells with acquired carfilzomib resistance. Chromatin immunoprecipitations indicated that endogenous KLF4 bound to the promoter regions of the SQSTM1 gene encoding the ubiquitin-binding adaptor protein sequestosome/p62 that links the proteasomal and autophagic protein degradation pathways. Ectopic expression of KLF4 induced upregulation of SQSTM1. On the other hand, inhibitors of autophagy sensitized MM cells to carfilzomib, even in carfilzomib-resistant derivatives having increased expression of the multidrug resistance protein P-glycoprotein. Thus, we report here a novel function for KLF4, one of the Yamanaka reprogramming factors, as being a contributor to autophagy gene expression which moderates preclinical proteasome inhibitor efficacy in MM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.