ArticleNature communications2021
Targeting NSD2-mediated SRC-3 liquid-liquid phase separation sensitizes bortezomib treatment in multiple myeloma.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 70 citations in OpenAlex.
- Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.Bone research · 2026Review
- Functionalized Coacervates for Cancer Therapy: Advances and Prospects in Phase-Separation-Based Intelligent Drug Delivery.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Small molecules modulate the biomolecular condensates and liquid‒liquid phase separation.Acta pharmaceutica Sinica. B · 2026Review
- Liquid-liquid phase separation in cancer therapy resistance.iScience · 2026Review
- Many faces of mammalian NSD methyltransferases.Cellular & molecular biology letters · 2026Review
- Liquid-Liquid Phase Separation in Cancer Drug Resistance: Mechanisms and Therapeutic Opportunities.Oncology research · 2026Review
- Steroid receptor coactivator-1: integrating steroid hormone signals to regulate brain function and disease.Frontiers in neuroscience · 2026Review
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- Targeting the Liquid-Liquid Separation Region of c-Maf for Treating Chromosomal Translocations in Multiple Myeloma.MedComm · 2025Article
- Mechanisms and Pathological Significance of Liquid-Liquid Phase Separation in Bacteria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Membraneless Organelles and Phase Separation in Tumours: Mechanisms and Prospects.Cell proliferation · 2025Review
- Current perspectives in drug targeting intrinsically disordered proteins and biomolecular condensates.BMC biology · 2025Review
- Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Liquid-liquid phase separation: an emerging perspective on the tumorigenesis, progression, and treatment of tumors.Frontiers in immunology · 2025Review
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024Review
- Multilevel Regulation of NF-κB Signaling by NSD2 Suppresses Kras-Driven Pancreatic Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.International journal of molecular sciences · 2024Review
- Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.Oncogene · 2024Article
- Lead Compound Development of SRC-3 Inhibitors with Improved Pharmacokinetic Properties and Anticancer Efficacy.Journal of medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone H3 lysine 36 dimethylation (H3K36me2) modifications on promoters of anti-apoptotic genes. Targeting SRC-3 or interference of its interactions with NSD2 using a newly developed inhibitor, SI-2, sensitizes BTZ treatment and overcomes drug resistance both in vitro and in vivo. Taken together, our findings elucidate a previously unrecognized orchestration of SRC-3 and NSD2 in acquired drug resistance of MM and suggest that SI-2 may be efficacious for overcoming drug resistance in MM patients.
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