ArticleOncotarget2017
GLI1-mediated regulation of side population is responsible for drug resistance in gastric cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 30 citations in OpenAlex.
- PHGDH drives 5-FU chemoresistance in colorectal cancer through the Hedgehog signaling.Journal of experimental & clinical cancer research : CR · 2025Article
- Molecular Mechanism for Malignant Progression of Gastric Cancer Within the Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Article
- Review
- The critical role of circular RNAs in drug resistance in gastrointestinal cancers.Medical oncology (Northwood, London, England) · 2023Review
- Targeting hedgehog-driven mechanisms of drug-resistant cancers.Frontiers in molecular biosciences · 2023Review
- Restoration of miRNA-143 Expression Inhibits Growth and Migration of MKN-45 Gastric Cancer Cell Line.Advanced pharmaceutical bulletin · 2022Article
- Horizontal transfer of the stemness-related markers EZH2 and GLI1 by neuroblastoma-derived extracellular vesicles in stromal cells.Translational research : the journal of laboratory and clinical medicine · 2021Article
- Defining the Role of GLI/Hedgehog Signaling in Chemoresistance: Implications in Therapeutic Approaches.Cancers · 2021Review
- Review
- The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies.Frontiers in cell and developmental biology · 2021Review
- The Hedgehog signaling pathway promotes chemotherapy resistance via multidrug resistance protein 1 in ovarian cancer.Oncology reports · 2020Article
- Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma.Cancers · 2020Review
- Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial-mesenchymal transition of gastric cancer cells.Bioscience reports · 2020Article
- GLI1 Inhibitor SRI-38832 Attenuates Chemotherapeutic Resistance by Downregulating NBS1 Transcription in BRAFFrontiers in oncology · 2020Article
- Article
- Gastric Cancer Stem Cells: Mechanisms and Therapeutic Approaches.Yonsei medical journal · 2018Review
- Role of GLI Transcription Factors in Pathogenesis and Their Potential as New Therapeutic Targets.International journal of molecular sciences · 2018Review
- Identification and validation of a Hedgehog pathway-based 3-gene prognostic signature for gastric cancers.Oncology letters · 2018Article
- Bioinformatic Analysis of GLI1 and Related Signaling Pathways in Chemosensitivity of Gastric Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Chemotherapy is frequently used for gastric cancer treatment. Most patients with advanced gastric cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. Thus, identifying molecular mechanisms responsible for cancer relapse following chemotherapy will help design new ways to treat gastric cancer. In this study, we revealed that the residual cancer cells following treatment with chemotherapeutic reagent cisplatin have elevated expression of hedgehog target genes GLI1, GLI2 and PTCH1, suggestive of hedgehog signaling activation. We showed that GLI1 knockdown sensitized gastric cancer cells to CDDP whereas ectopic GLI1 expression decreased the sensitivity. Further analyses indicate elevated GLI1 expression is associated with an increase in tumor sphere formation, side population and cell surface markers for putative cancer stem cells. We have evidence to support that GLI1 is critical for maintenance of putative cancer stem cells through direct regulation of ABCG2. In fact, GLI1 protein was shown to be associated with the promoter fragment of ABCG2 through a Gli-binding consensus site in gastric cancer cells. Disruption of ABCG2 function, through ectopic expression of an ABCG2 dominant negative construct or a specific ABCG2 inhibitor, increased drug sensitivity of cancer cells both in culture and in mice. The relevance of our studies to gastric cancer patient care is reflected by our discovery that high ABCG2 expression was associated with poor survival in the gastric cancer patients who underwent chemotherapy. Taken together, we have identified a molecular mechanism by which gastric cancer cells gain chemotherapy resistance.
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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.