ArticlePLoS biology2013
Sonic Hedgehog promotes tumor cell survival by inhibiting CDON pro-apoptotic activity.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 60 citations in OpenAlex.
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- PIEZO2 in tumors: from mechanobiological switches to activity-targeted therapies.Journal of experimental & clinical cancer research : CR · 2025Review
- Plasma proteomic and polygenic profiling improve risk stratification and personalized screening for colorectal cancer.Nature communications · 2024Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1.Nature communications · 2024Article
- LowCancers · 2024Article
- Therapeutic implication of Sonic Hedgehog as a potential modulator in ischemic injury.Pharmacological reports : PR · 2023Review
- Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma.Nature communications · 2023Article
- Persistent Properties of a Subpopulation of Cancer Cells Overexpressing the Hedgehog Receptor Patched.Pharmaceutics · 2022Article
- Transcriptome sequencing reveals a lncRNA-mRNA interaction network in extramammary Paget's disease.BMC medical genomics · 2021Article
- Dependence receptors: new targets for cancer therapy.EMBO molecular medicine · 2021Review
- ZSWIM8 is a myogenic protein that partly prevents C2C12 differentiation.Scientific reports · 2021Article
- Targeting netrin-3 in small cell lung cancer and neuroblastoma.EMBO molecular medicine · 2021Article
- Hedgehog Signaling in Colorectal Cancer: All in the Stroma?International journal of molecular sciences · 2021Review
- Blocking SHH/Patched Interaction Triggers Tumor Growth Inhibition through Patched-Induced Apoptosis.Cancer research · 2020Article
- Article
- Kremen1-induced cell death is regulated by homo- and heterodimerization.Cell death discovery · 2019Article
- Review
- Modulation of sonic hedgehog-induced mouse embryonic stem cell behaviours through E-cadherin expression and integrin β1-dependent F-actin formation.British journal of pharmacology · 2018Article
- Regulation of Hedgehog Signaling in Cancer by Natural and Dietary Compounds.Molecular nutrition & food research · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hedgehog signaling is a determinant pathway for tumor progression. However, while inhibition of the Hedgehog canonical pathway-Patched-Smoothened-Gli-has proved efficient in human tumors with activating mutations in this pathway, recent clinical data have failed to show any benefit in other cancers, even though Sonic Hedgehog (SHH) expression is detected in these cancers. Cell-adhesion molecule-related/down-regulated by Oncogenes (CDON), a positive regulator of skeletal muscle development, was recently identified as a receptor for SHH. We show here that CDON behaves as a SHH dependence receptor: it actively triggers apoptosis in the absence of SHH. The pro-apoptotic activity of unbound CDON requires a proteolytic cleavage in its intracellular domain, allowing the recruitment and activation of caspase-9. We show that by inducing apoptosis in settings of SHH limitation, CDON expression constrains tumor progression, and as such, decreased CDON expression observed in a large fraction of human colorectal cancer is associated in mice with intestinal tumor progression. Reciprocally, we propose that the SHH expression, detected in human cancers and previously considered as a mechanism for activation of the canonical pathway in an autocrine or paracrine manner, actually provides a selective tumor growth advantage by blocking CDON-induced apoptosis. In support of this notion, we present the preclinical demonstration that interference with the SHH-CDON interaction triggers a CDON-dependent apoptosis in vitro and tumor growth inhibition in vivo. The latter observation qualifies CDON as a relevant alternative target for anticancer therapy in SHH-expressing tumors.
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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.