ArticleOncotarget2015
Inhibition of EP2/EP4 signaling abrogates IGF-1R-mediated cancer cell growth: involvement of protein kinase C-θ activation.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Overview of Prostaglandin E2 (PGE2)-Targeting Radiolabelled Imaging Probes from Preclinical Perspective: Lessons Learned and Road Ahead.International journal of molecular sciences · 2023Review
- Insulin-like growth factor-1 stimulates retinal cell proliferation via activation of multiple signaling pathways.Current research in neurobiology · 2023Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Inhibition of EP2 receptor suppresses tumor growth and chemoresistance of gastric cancer.American journal of cancer research · 2022Article
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- GPCRs in pancreatic adenocarcinoma: Contributors to tumour biology and novel therapeutic targets.British journal of pharmacology · 2020Review
- GRK2 Suppresses Hepatocellular Carcinoma Metastasis and Invasion Through Down-Regulation of Prostaglandin E Receptor 2.OncoTargets and therapy · 2020Article
- Eicosanoids in Cancer: Prostaglandin EFrontiers in pharmacology · 2020Review
- Insulin-like growth factor-1 receptor knockdown enhances radiosensitivity via the HIF-1α pathway and attenuates ATM/H2AX/53BP1 DNA repair activation in human lung squamous carcinoma cells.Oncology letters · 2018Article
- Targeting EP4 downstream c-Jun through ERK1/2-mediated reduction of DNMT1 reveals novel mechanism of solamargine-inhibited growth of lung cancer cells.Journal of cellular and molecular medicine · 2017Article
- Inactivation of PI3-K/Akt and reduction of SP1 and p65 expression increase the effect of solamargine on suppressing EP4 expression in human lung cancer cells.Journal of experimental & clinical cancer research : CR · 2015Article
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Associations between growth factor receptor-mediated cell signaling and cancer cell growth have been previously characterized. Receptors for prostaglandin E2, such as EP2, and EP4, play roles in cancer growth, progression and invasion. Thus, we examined the interactions between EP2/EP4- and IGF-1R-mediated cellular signaling in human pancreatic cancer cells. Selective antagonists against EP2 and EP4 abrogated IGF-1-stimulated cell growth and suppressed MEK/ERK phosphorylation. In subsequent experiments, phospho-antibody arrays indicated increased phosphorylation levels of protein kinase C-θ (PKC-θ) at the Thr538 position following the inhibition of EP2/EP4-mediated signaling. Inhibition of PKC-θ activity impaired cell viability compared with EP2/EP4-antagonized IGF-1-stimulated cells. PKC-θ kinase MAP4K3, which plays a pivotal role in PKC-θ activation, also affected growth signaling in the presence of EP2/EP4 antagonists. Administration of EP2 and EP4 antagonists significantly inhibited the growth of an orthotopic xenograft of IGF-1-secreting pancreatic cancer cells, with increased phospho-PKC-θ and decreased phospho-ERK. Clinico-pathological analyses showed that 17.4% of surgical pancreatic cancer specimens were quadruple-positive for IGF-1R, EP2 (or EP4), MAP4K3, and PKC-θ. These results indicate a novel signaling crosstalk between EP2/EP4 and IGF-1R in cancer cells, and suggest that the MAP4K3-PKC-θ axis is central and could be exploited as a molecular target for cancer therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.