ArticleOncogene2017
The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 57 citations in OpenAlex.
- Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development.Signal transduction and targeted therapy · 2021Trial
- Network-based single-cell analysis identifies a proliferative GZMBJournal of translational medicine · 2026Article
- Targeted Therapy and Immunotherapies in Hepatocellular Carcinoma: Mechanisms and Clinical Studies.MedComm · 2026Review
- Autophagy-Targeting Stapled Peptide Utilizes Macropinocytosis for Cell Entry to Potentiate Anti-Proliferative Autosis in Small-Cell Lung Cancer.Pharmaceutics · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays.Biochimica et biophysica acta. General subjects · 2024Article
- Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumors.Frontiers in oncology · 2024Article
- Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype.Oncogene · 2023Article
- Molecular and clonal evolutioniScience · 2023Article
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Genomic alterations of oligodendrogliomas at distant recurrence.Cancer medicine · 2023Article
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- Canonical Hedgehog Pathway and Noncanonical GLI Transcription Factor Activation in Cancer.Cells · 2022Review
- The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery.Cancers · 2022Review
- Lung Cancer Stem Cell Markers as Therapeutic Targets: An Update on Signaling Pathways and Therapies.Frontiers in oncology · 2022Review
- The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time.International journal of molecular sciences · 2021Review
- MicroRNA miR-19b-3p mediated G protein γ subunit 7 (GNG7) loss contributes lung adenocarcinoma progression through activating Hedgehog signaling.Bioengineered · 2021Article
- Genetic variants in the Hedgehog signaling pathway genes are associated with gastric cancer risk in a Chinese Han population.Journal of biomedical research · 2021Article
- Review
- Hedgehog/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease.Cancers · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations. In particular, the existence of autocrine, ligand-dependent Hh signaling in SCLC has been disputed. In a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand Sonic Hedgehog (Shh) for the progression of SCLC. Conversely, we show that conditional Shh overexpression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression. When compared to mouse SCLC tumors expressing an activating, ligand-independent Smo mutant, tumors overexpressing Shh exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a putative non-canonical arm of the Hh pathway. In turn, we show that overexpression of Cyclin B1 induces chromosomal instability in mouse embryonic fibroblasts lacking both Tp53 and Rb1. These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability.
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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.