ArticleBlood2012
Canonical and noncanonical Hedgehog pathway in the pathogenesis of multiple myeloma.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Predicting treatment benefit in multiple myeloma through simulation of alternative treatment effects.Nature communications · 2018Trial
- Integrating Single-Cell Sequencing and Proteomics to Unravel Stem Cell Heterogeneity: Implications for Precision Regenerative Medicine.Stem cell reviews and reports · 2026Review
- The role of KPNA3 in multiple myeloma: implications for targeting nuclear import.Apoptosis : an international journal on programmed cell death · 2026Article
- Uncovering the role of integrated stress in Alzheimer's disease through single-cell and transcriptomic analysis.Scientific reports · 2026Article
- Brain transcriptomics highlight abundant gene expression and splicing alterations in non-neuronal cells in aFTLD-U.Acta neuropathologica · 2025Article
- Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of LSD1 and OXPHOS.Cell reports · 2025Article
- Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword.Cancer cell international · 2025Review
- Increased expression of PTCH1 and GLI1 in Bangladeshi TNBC Patients after Treatment with Doxorubicin and Cyclophosphamide Suggests a Favorable Response to Chemotherapy.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- The molecular features of lung cancer stem cells in dedifferentiation process-driven epigenetic alterations.The Journal of biological chemistry · 2024Review
- Molecular insights into the hedgehog signaling pathway correlated non-coding RNAs in acute lymphoblastic leukemia, a bioinformatics study.Annals of hematology · 2024Article
- Distinct pathway activities are associated with prognosis and response to bortezomib-containing treatment in MCL1-M based molecular subtypes of multiple myeloma.Annals of hematology · 2024Article
- Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.Molecular brain · 2024Review
- Interactions between hedgehog signaling pathway and the complex tumor microenvironment in breast cancer: current knowledge and therapeutic promises.Cell communication and signaling : CCS · 2024Review
- Article
- Current Status of Hedgehog Signaling Inhibitors.Current topics in medicinal chemistry · 2024Review
- Evaluation of Expression of WNT1 and PTCH Genes in Peripheral Blood of Patients with Odontogenic Cysts and Tumours of the Jaws by Quantitative RT-PCR: A Pilot Study.Journal of maxillofacial and oral surgery · 2023Article
- TP53BP2: Roles in suppressing tumorigenesis and therapeutic opportunities.Genes & diseases · 2023Review
- Regulation of miRNA expression by α4β1 integrin-dependent multiple myeloma cell adhesion.EJHaem · 2023Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
The Hedgehog (Hh) pathway is required for cell-fate determination during the embryonic life, as well as cell growth and differentiation in the adult organism, where the inappropriate activation has been implicated in several cancers. Here we demonstrate that Hh signaling plays a significant role in growth and survival of multiple myeloma (MM) cells. We observed that CD138(+) MM cells express Hh genes and confirmed Smoothened (Smo)-dependent Hh signaling in MM using a novel synthetic Smo inhibitor, NVP-LDE225 (Novartis), which decreased MM cell viability by inducing specific down-regulation of Gli1 and Ptch1, hallmarks of Hh activity. In addition, we detected a nuclear localization of Gli1 in MM cells, which is completely abrogated by Forskolin, a Gli1-modulating compound, confirming Smo-independent mechanisms leading to Hh activation in MM. Finally, we identified that bone marrow stromal cells are a source of the Shh ligand, although they are resistant to the Hh inhibitor because of defective Smo expression and Ptch1 up-regulation. Further in vitro as well as in vivo studies showed antitumor efficacy of NVP-LDE225 in combination with bortezomib. Altogether, our data demonstrate activation of both canonical and noncanonical Hh pathway in MM, thus providing the rationale for testing Hh inhibitors in clinical trials to improve MM patient outcome.
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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.