ArticleBlood2014
A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 99 citations in OpenAlex.
- The role of KPNA3 in multiple myeloma: implications for targeting nuclear import.Apoptosis : an international journal on programmed cell death · 2026Article
- The progression of multiple myeloma is regulated by LILRB1 via the GATA2-SAGE1 pathway.British journal of haematology · 2025Article
- Genetic, epigenetic, and molecular determinants of multiple myeloma and precursor plasma cell disorders: a pathophysiological overview.Medical oncology (Northwood, London, England) · 2025Review
- Conserved C143 forms a branched intermediate in Hedgehog autoprocessing: A cancer drug discovery target against Hedgehog signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nestin in multiple myeloma: emerging insights into a potential therapeutic target.Frontiers in oncology · 2025Review
- MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma: a preliminary study.Frontiers in pharmacology · 2025Article
- NAT10 MediatesJournal of Cancer · 2024Article
- Focal adhesion kinase as a new player in the biology of onco-hematological diseases: the starting evidence.Frontiers in oncology · 2024Review
- Acetylcytidine modification of DDX41 and ZNF746 byFrontiers in oncology · 2024Article
- All-trans retinoic acid improves NSD2-mediated RARα phase separation and efficacy of anti-CD38 CAR T-cell therapy in multiple myeloma.Journal for immunotherapy of cancer · 2023Article
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- Molecular and immunological mechanisms of clonal evolution in multiple myeloma.Frontiers in immunology · 2023Review
- Targeting hedgehog-driven mechanisms of drug-resistant cancers.Frontiers in molecular biosciences · 2023Review
- Noncanonical Sonic Hedgehog signaling amplifies platelet reactivity and thrombogenicity.Blood advances · 2022Article
- Nanomolar, Noncovalent Antagonism of Hedgehog Cholesterolysis: Exception to the "Irreversibility Rule" for Protein Autoprocessing Inhibition.Biochemistry · 2022Article
- Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives.Molecular cancer · 2022Review
- Posttranslational modification of Aurora A-NSD2 loop contributes to drug resistance in t(4;14) multiple myeloma.Clinical and translational medicine · 2022Article
- Epigenomic reprogramming via HRP2-MINA dictates response to proteasome inhibitors in multiple myeloma with t(4;14) translocation.The Journal of clinical investigation · 2022Article
- Hedgehog Autoprocessing: From Structural Mechanisms to Drug Discovery.Frontiers in molecular biosciences · 2022Review
- Hedgehog/GLI signaling in hematopoietic development and acute myeloid leukemia-From bench to bedside.Frontiers in cell and developmental biology · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Hedgehog (Hh) signaling plays an important role in the oncogenesis of B-cell malignancies such as multiple myeloma (MM). However, the source of Hh ligand sonic hedgehog (SHH) and its target cells remains controversial. Previous studies showed that stromally induced Hh signaling is essential for the tumor cells and that CD19(+)CD138(-) MM stem cells are the target cells of Hh signaling. Here we demonstrate that SHH was mainly secreted by human myeloma cells but not by stromal cells in MM bone marrow. Autocrine SHH enhanced CD138(+) myeloma cell proliferation and protected myeloma cells from spontaneous and stress-induced apoptosis. More importantly, autocrine SHH protected myeloma cells against chemotherapy-induced apoptosis in vitro and in vivo. Combinational treatment with chemotherapy and SHH-neutralizing antibody displayed synergistic antimyeloma effects. Mechanistic studies showed that SHH signaling activated the SHH/GLI1/BCL-2 axis, leading to the inhibition of myeloma cell apoptosis. Thus, this study identifies the myeloma autocrine Hh signaling pathway as a potential target for the treatment of MM. Targeting this pathway may improve the efficacy of chemotherapy in MM patients.
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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.