ArticleJournal of experimental & clinical cancer research : CR2017
YAP transcriptionally regulates COX-2 expression and GCCSysm-4 (G-4), a dual YAP/COX-2 inhibitor, overcomes drug resistance in colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Regulation of lipid droplets accumulation by the Hippo-YAP/COX2 signaling pathway in neomycin-induced ototoxicity.Cell death discovery · 2026Article
- T-cell-targeted immunotherapy in neurofibromatosis type 2-related vestibular schwannoma: current evidence and future direction.Brain communications · 2026Review
- Triptonide-mediated PTGS2 Inhibition Induces Autophagic Cell Death to Suppress the Progression of Triple-negative Breast Cancer and Epithelial Ovarian Cancer.International journal of biological sciences · 2026Article
- A pH-sensitive peptide amphiphilic-based drug delivery system inhibits hepatocellular carcinoma growth by suppressing hepatic stellate cell activation.Materials today. Bio · 2025Article
- Outer membrane vesicles of Porphyromonas gingivalis impede bone regeneration by inducing ferroptosis via the Hippo-YAP signaling pathway.Journal of nanobiotechnology · 2025Article
- Hippo/YAP signaling pathway in colorectal cancer: regulatory mechanisms and potential drug exploration.Frontiers in oncology · 2025Review
- COX-2 in lung cancer: Mechanisms, development, and targeted therapies.Chronic diseases and translational medicine · 2024Review
- Review
- Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer.Cell discovery · 2024Article
- Long noncoding RNA MALAT-1: A versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance.Non-coding RNA research · 2024Review
- RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway.Journal of clinical and translational hepatology · 2024Article
- Role of YAP Signaling in Regulation of Programmed Cell Death and Drug Resistance in Cancer.International journal of biological sciences · 2024Review
- ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism.Nature chemical biology · 2023Article
- Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis.Cancers · 2023Review
- New insights into the ambivalent role of YAP/TAZ in human cancers.Journal of experimental & clinical cancer research : CR · 2023Review
- Preventive Effect of Pharmaceutical Phytochemicals Targeting the Src Family of Protein Tyrosine Kinases and Aryl Hydrocarbon Receptor on Environmental Stress-Induced Skin Disease.International journal of molecular sciences · 2023Review
- Analytical validation of the 7-gene biosignature for prediction of recurrence risk and radiation therapy benefit for breast ductal carcinomaFrontiers in oncology · 2023Article
- YAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro.Nature communications · 2022Article
- Mutant p53, the Mevalonate Pathway and the Tumor Microenvironment Regulate Tumor Response to Statin Therapy.Cancers · 2022Review
- Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemotherapy resistance remains a major challenge in cancer treatment. COX-2 (cyclooxygenase 2) is involved in drug resistance and poor prognosis of many neoplastic diseases or cancers. However, investigations identifying new modulators of COX-2 pathway and searching for new chemicals targeting these valid resistant biomarkers are still greatly needed.
methodsHCT15, HCT-116, HT-29, COLO205, FHC, IMCE, SW480 cell lines were used to detect the expression of YAP and COX-2. Site-directed mutagenesis, luciferase reporter analysis and ChIP assay were used to test whether YAP activated COX-2 transcription through interaction with TEAD binding sites in the promoter of COX-2. Cell line models exhibiting overexpression or knockdown of some genes were generated using transfection agents. Coimmunoprecipitation was used to detect protein mutual interaction. mRNA and protein levels were measured by qRT-PCR and western blot respectively.
resultsHere, we reported that both YAP and COX-2 were overexpressed in colorectal cancer cells. YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. YAP conferred drug resistance through COX-2 and its related effectors such as MCL, MDR, Survivin. GCCSysm-4 (G-4), a YAP and COX-2 inhibitor, effectively inhibited both YAP and COX-2 activation, induced apoptosis and decreased viability in Taxol-resistant cells. Inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the resistance of CRC cells than either of them alone.
conclusionsOur data provide new mechanisms that YAP is a new upstream regulator of COX-2 pathway and plays an important role in conferring resistance in CRC cells. G-4, targeting YAP-COX-2, may be a novel valuable strategy to combat resistance in CRC.
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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.