ArticleJournal of experimental & clinical cancer research : CR2016
Autocrine Sonic hedgehog signaling promotes gastric cancer proliferation through induction of phospholipase Cγ1 and the ERK1/2 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- MAPK/ERK signaling pathway in rheumatoid arthritis: mechanisms and therapeutic potential.PeerJ · 2025Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- Landscape of Druggable Molecular Pathways Downstream of Genomic CDH1/Cadherin-1 Alterations in Gastric Cancer.Journal of personalized medicine · 2022Article
- Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives.Molecular cancer · 2022Review
- Ferroptosis Mediation Patterns Reveal Novel Tool to Implicate Immunotherapy and Multi-Omics Characteristics in Bladder Cancer.Frontiers in cell and developmental biology · 2022Article
- Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment.Acta pharmaceutica Sinica. B · 2021Review
- Clinical and prognostic significances of cancer stem cell markers in gastric cancer patients: a systematic review and meta-analysis.Cancer cell international · 2021Review
- Knockdown of TRIM37 Promotes Apoptosis and Suppresses Tumor Growth in Gastric Cancer by Inactivation of the ERK1/2 Pathway.OncoTargets and therapy · 2020Article
- Sonic Hedgehog Protein is Frequently Up-Regulated in Pancreatic Cancer Compared to Colorectal Cancer.Pathology oncology research : POR · 2020Article
- The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2019Article
- Hedgehog Signaling: An Achilles' Heel in Cancer.Translational oncology · 2019Review
- LIFR-AS1 modulates Sufu to inhibit cell proliferation and migration by miR-197-3p in breast cancer.Bioscience reports · 2019Article
- Protective potential of miR-146a-5p and its underlying molecular mechanism in diverse cancers: a comprehensive meta-analysis and bioinformatics analysis.Cancer cell international · 2019Article
- The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia.Molecular biology of the cell · 2018Article
- Targeting GLI Transcription Factors in Cancer.Molecules (Basel, Switzerland) · 2018Review
- Inhibition of Hedgehog signaling suppresses proliferation and microcyst formation of human Autosomal Dominant Polycystic Kidney Disease cells.Scientific reports · 2018Article
- Review
- Sonic Hedgehog Signaling Pathway Mediates Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid ArthritisFrontiers in immunology · 2018Article
- Antagonism between Hedgehog and Wnt signaling pathways regulates tumorigenicity.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSonic hedgehog (SHH) plays critical roles in cell growth and development. Tumor cells express SHH, which can promote cell proliferation and epithelial-to-mesenchymal transition. However, the autocrine SHH pathway has not been described in gastric cancer. The aim of this study was to explore molecular mechanisms underlying autocrine SHH signaling in gastric cancer cells.
methodsSHH expression was assessed using immunohistochemistry and the results were compared with clinicopathologic parameters, including survival. Using gastric cancer cell lines, we measured SHH mRNA and protein expression, and studied the effects of SHH signaling on cell proliferation and SHH secretion. We also studied the effects of an inhibitor of PLC-γ1 on phosphorylation of phospholipase Cγ1 and extracellular signal-regulated kinases (ERK)1/2.
resultsSHH protein expression in gastric cancer tissue was significantly higher compared with that in normal gastric tissue (P < 0.001), and the increased expression was significantly associated with pT staging (P = 0.004), pN staging (P = 0.018), pM staging (P = 0.006), and pTNM staging (P < 0.001). In multivariate analyses, overall survival in gastric cancer was significantly shorter in cases with high SHH expression (HR = 1.734, 95% CI: 1.109-2.713, P = 0.016). The AGS and SGC-7901 gastric cancer cell lines expressed SHH mRNA and protein. In these cell lines, SHH promoted carcinogenesis through activation of the PLCγ1-ERK1/2 pathway, resulting in increased cell proliferation and survival.
conclusionsIncreased SHH expression is associated with shorter survival in gastric cancer patients, and SHH could represent a useful biomarker or therapeutic target for this disease.
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