ArticleOncotarget2016
Hedgehog pathway maintains cell survival under stress conditions, and drives drug resistance in lung adenocarcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Comparative Response of Canine and Human Osteosarcoma Tumour Cell Lines to Molecularly Targeted Anticancer Agents at Clinically Relevant Exposures With Analysis of Genomic Biomarkers.Veterinary and comparative oncology · 2026Article
- Breathing new life into the study of COPD with genes identified from genome-wide association studies.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma.Clinical epigenetics · 2023Article
- Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.Frontiers in oncology · 2022Review
- miR‑367‑3p downregulates Rab23 expression and inhibits Hedgehog signaling resulting in the inhibition of the proliferation, migration, and invasion of prostate cancer cells.Oncology reports · 2021Article
- Responsiveness to Hedgehog Pathway Inhibitors in T-Cell Acute Lymphoblastic Leukemia Cells Is Highly Dependent on 5'AMP-Activated Kinase Inactivation.International journal of molecular sciences · 2021Article
- Downregulation of hedgehog-interacting protein (HHIP) contributes to hexavalent chromium-induced malignant transformation of human bronchial epithelial cells.Carcinogenesis · 2021Article
- HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas.Genes · 2021Article
- Article
- NRF2 and Primary Cilia: An Emerging Partnership.Antioxidants (Basel, Switzerland) · 2020Review
- Transposable elements contribute to the genomic response to insecticides inPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Article
- NRF2-dependent gene expression promotes ciliogenesis and Hedgehog signaling.Scientific reports · 2019Article
- MicroRNA-122 negatively associates with peroxiredoxin-II expression in human gefitinib-resistant lung cancer stem cells.Cancer gene therapy · 2019Article
- Pigment epithelium-derived factor peptide promotes limbal stem cell proliferation through hedgehog pathway.Journal of cellular and molecular medicine · 2019Article
- Epigenetic heterogeneity in cancer.Biomarker research · 2019Review
- HHIP overexpression inhibits the proliferation, migration and invasion of non-small cell lung cancer.PloS one · 2019Article
- Hedgehog Signaling in Lung Cancer: From Oncogenesis to Cancer Treatment Resistance.International journal of molecular sciences · 2018Review
- Review
- Targeting EHMT2 reverses EGFR-TKI resistance in NSCLC by epigenetically regulating the PTEN/AKT signaling pathway.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog (HH) pathway plays an important role in embryonic development, but is largely inactive in adult except for tissue repair. Aberrant activation of HH pathway has been found in a variety of cancer types. In non-small cell lung cancer, however, the role and importance of HH pathway remain controversial. In the current study, we found that HH pathway was maintained in low activity in lung adenocarcinoma (LAC) cells under normal culture condition, but was highly induced in response to stress conditions. Activation of HH pathway promoted cell survival, growth, and invasion partially through HGF and MET signaling. Hedgehog-Interacting Protein (HHIP), a cell-surface negative regulator of HH pathway, was epigenetically silenced in LAC. Overexpression of HHIP blocked the activation of HH and HGF/MET pathways, and made cells significantly more susceptible to stress conditions. In LAC cells with acquired resistance to Epidermal Growth Factor Receptor Tyrosin Kinase Inhibitor (EGFR-TKI), we found that a part of tumor cells were much more sensitive to HH or HGF/MET inhibitors, suggesting an oncogenic addiction shift from EGFR to HH and HGF/MET pathways. In conclusion, this study showed that HH pathway is a survival signaling that drives LAC cell growth under stress conditions, and HHIP is a key regulator to block the induction of HH pathway. Targeting the HH pathway through inhibitors or HHIP thus holds promise to address EGFR-TKI resistance in LAC in clinic.
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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.