ArticleNature medicine2016
Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 181 citations in OpenAlex.
- Trial
- Trial
- Lenalidomide, adriamycin, dexamethasone for induction followed by stem-cell transplant in newly diagnosed myeloma.Leukemia · 2017Trial
- Trial
- Activating RARβ to overcome immunomodulatory drug resistance in t(4;14) human myeloma.Leukemia · 2026Article
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- β-Elemene Rescues Radiation-Induced Enteritis by Orchestrating a Host-Microbiome Circuit That Fuels Epigenetic DNA Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SLC16A1 Activates the STAT3/SLC7A11 Pathway to Mediate Ferroptosis Resistance and Tumor Progression in Head and Neck Squamous Cell Carcinoma.Oncology research · 2026Article
- Label-free protein-structure-sensitive live-cell microscopy for patient-specific assessment of myeloma therapy.Nature biomedical engineering · 2026Article
- Epigenetic regulation of Cereblon in cancer: molecular mechanisms and clinical implications.Genes & genomics · 2025Article
- Serum Cereblon (CRBN) Levels Predict Long Term Post- Lenalidomide-Dexamethasone Survival in Multiple Myeloma (MM) Patients and Correlate with Disease Characteristics.International journal of molecular sciences · 2025Article
- A basigin antibody modulates MCTs to impact tumor metabolism and immunity.Cell discovery · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome.Cell communication and signaling : CCS · 2025Article
- Lactate metabolism in clonal plasma cells and its therapeutic implications in multiple myeloma patients with elevated serum LDH levels.Cancer & metabolism · 2025Article
- Enhanced Bioavailability of a Thionated IMiD Derivative Nanosuspension for Parkinson's Disease Targeting α-Synuclein.International journal of nanomedicine · 2025Article
- Metabolic Function and Therapeutic Potential of CD147 for Hematological Malignancies: An Overview.International journal of molecular sciences · 2024Review
- Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma.Biomolecules · 2024Article
- The CBEMBO molecular medicine · 2024Article
- Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription.Clinical and translational medicine · 2024Review
44 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 11 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Here we identify a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147-MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. We found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147-MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, we show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs.
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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.