ArticleLeukemia2016
Blocking the ZZ domain of sequestosome1/p62 suppresses myeloma growth and osteoclast formation in vitro and induces dramatic bone formation in myeloma-bearing bones in vivo.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Sequestosome-1/p62 Mediates TLR4-Induced Inflammatory Program in Dendritic Cells Under Normoxic and Hypoxic Conditions.Cellular and molecular life sciences : CMLS · 2025Article
- GCN-BBB: Deep Learning Blood-Brain Barrier (BBB) Permeability PharmacoAnalytics with Graph Convolutional Neural (GCN) Network.The AAPS journal · 2025Article
- p62/SQSTM1 in cancer: phenomena, mechanisms, and regulation in DNA damage repair.Cancer metastasis reviews · 2025Review
- Current Understanding of the Role of Autophagy in the Treatment of Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Pharmacologic targeting of the p62 ZZ domain enhances both anti-tumor and bone-anabolic effects of bortezomib in multiple myeloma.Haematologica · 2024Article
- SQSTM1/p62 promotes the progression of gastric cancer through epithelial-mesenchymal transition.Heliyon · 2024Article
- The PB1 and the ZZ domain of the autophagy receptor p62/SQSTM1 regulate the interaction of p62/SQSTM1 with the autophagosome protein LC3B.Protein science : a publication of the Protein Society · 2024Article
- Article
- Dusquetide modulates innate immune response through binding to p62.Structure (London, England : 1993) · 2022Article
- Pathogenesis and treatment of multiple myeloma bone disease.The Japanese dental science review · 2021Review
- Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).International journal of oncology · 2021Review
- Review
- Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression.Cancers · 2021Review
- TAK1 is a pivotal therapeutic target for tumor progression and bone destruction in myeloma.Haematologica · 2021Article
- Summary of the 2019 Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020Review
- Structure-Based Design of Novel Biphenyl Amide Antagonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 8 Channels with Potential Implications in the Treatment of Sensory Neuropathies.ACS chemical neuroscience · 2020Article
- SQSTM1/p62: A Potential Target for Neurodegenerative Disease.ACS chemical neuroscience · 2019Review
- Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts.Oncotarget · 2019Article
- Epigenetic-Based Mechanisms of Osteoblast Suppression in Multiple Myeloma Bone Disease.JBMR plus · 2019Review
- Osteoblast suppression in multiple myeloma bone disease.Journal of bone oncology · 2018Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
We reported that p62 (sequestosome 1) serves as a signaling hub in bone marrow stromal cells (BMSCs) for the formation of signaling complexes, including NFκB, p38MAPK and JNK, that are involved in the increased osteoclastogenesis and multiple myeloma (MM) cell growth induced by BMSCs that are key contributors to multiple myeloma bone disease (MMBD), and demonstrated that the ZZ domain of p62 (p62-ZZ) is required for BMSC enhancement of MMBD. We recently identified a novel p62-ZZ inhibitor, XRK3F2, which inhibits MM cell growth and BMSC growth enhancement of human MM cells. In the current study, we evaluate the relative specificity of XRK3F2 for p62-ZZ, characterize XRK3F2's capacity to inhibit growth of primary MM cells and human MM cell lines, and test the in vivo effects of XRK3F2 in the immunocompetent 5TGM1 MM model. We found that XRK3F2 induces dramatic cortical bone formation that is restricted to MM containing bones and blocked the effects and upregulation of tumor necrosis factor alpha (TNFα), an osteoblast (OB) differentiation inhibitor that is increased in the MM bone marrow microenvironment and utilizes signaling complexes formed on p62-ZZ, in BMSC. Interestingly, XRK3F2 had no effect on non-MM bearing bone. These results demonstrate that targeting p62 in MM models has profound effects on MMBD.
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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.