ArticlePloS one2013
Gli1 mediates lung cancer cell proliferation and Sonic Hedgehog-dependent mesenchymal cell activation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- The Role of Hedgehog Signaling in Non-small Cell Lung Cancer: Targeting Tumor Invasion, Therapy Resistance and Novel Therapeutic Strategies.International journal of biological sciences · 2026Review
- Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting.Nature communications · 2025Article
- Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting.bioRxiv : the preprint server for biology · 2025Article
- SMARCB1-driven EGFR-GLI1 epigenetic alterations in lung cancer progression and therapy are differentially modulated by MEOX2 and GLI-1.Cancer gene therapy · 2025Article
- Mechanisms and therapeutic potential of the hedgehog signaling pathway in cancer.Cell death discovery · 2025Review
- Multiple signaling pathways in the frontiers of lung cancer progression.Frontiers in immunology · 2025Review
- Influence of intersignaling crosstalk on the intracellular localization of YAP/TAZ in lung cells.Cell communication and signaling : CCS · 2024Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Expression analysis and regulation of GLI and its correlation with stemness and metabolic alteration in human brain tumor.3 Biotech · 2023Article
- Cancer-associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications.International journal of cancer · 2022Review
- Review
- Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.Frontiers in oncology · 2022Review
- HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas.Genes · 2021Article
- High Circulating Sonic Hedgehog Protein Is Associated With Poor Outcome in EGFR-Mutated Advanced NSCLC Treated With Tyrosine Kinase Inhibitors.Frontiers in oncology · 2021Article
- Natural products remodel cancer-associated fibroblasts in desmoplastic tumors.Acta pharmaceutica Sinica. B · 2020Review
- Stromal Hedgehog pathway activation by IHH suppresses lung adenocarcinoma growth and metastasis by limiting reactive oxygen species.Oncogene · 2020Article
- Article
- Possible correlation of sonic hedgehog signaling with epithelial-mesenchymal transition in muscle-invasive bladder cancer progression.Journal of cancer research and clinical oncology · 2019Article
- Review
- Patched homolog 1 (PTCHI) gene mutations can predict the outcome of chronic myeloid leukemia patients?American journal of blood research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-Small-Cell-Lung-Cancer (NSCLC) represents approximately 85% of all lung cancers and remains poorly understood. While signaling pathways operative during organ development, including Sonic Hedgehog (Shh) and associated Gli transcription factors (Gli1-3), have recently been found to be reactivated in NSCLC, their functional role remains unclear. Here, we hypothesized that Shh/Gli1-3 could mediate NSCLC autonomous proliferation and epithelial/stromal signaling in the tumoral tissue. In this context, we have investigated the activity of Shh/Gli1-3 signaling in NSCLC in both, cancer and stromal cells. We report here that inhibition of Shh signaling induces a significant decrease in the proliferation of NSCLC cells. This effect is mediated by Gli1 and Gli2, but not Gli3, through regulation of cyclin D1 and cyclin D2 expression. While exogenous Shh was unable to induce signaling in either A549 lung adenocarcinoma or H520 lung squamous carcinoma cells, both cells were found to secrete Shh ligand, which induced fibroblast proliferation, survival, migration, invasion, and collagen synthesis. Furthermore, Shh secreted by NSCLC mediates the production of proangiogenic and metastatic factors in lung fibroblasts. Our results thus provide evidence that Shh plays an important role in mediating epithelial/mesenchymal crosstalk in NSCLC. While autonomous Gli activity controls NSCLC proliferation, increased Shh expression by NSCLC is associated with fibroblast activation in tumor-associated stroma. Our study highlights the relevance of studying stromal-associated cells in the context of NSCLC regarding new prognosis and therapeutic options.
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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.