EP4 as a Therapeutic Target for Aggressive Human Breast Cancer

@article{Majumder2018EP4AA,
  title={EP4 as a Therapeutic Target for Aggressive Human Breast Cancer},
  author={Mousumi Majumder and Pinki Nandi and Ahmed Mohamed Omar and Kingsley Chukwunonso Ugwuagbo and Peeyush K. Lala},
  journal={International Journal of Molecular Sciences},
  year={2018},
  volume={19}
}
G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5′-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well… 

Figures from this paper

Eicosanoids in Cancer: Prostaglandin E2 Receptor 4 in Cancer Therapeutics and Immunotherapy

TLDR
There is growing evidence that EP4 antagonism, particularly in combination with either chemotherapy, endocrine therapy, or immune-based therapies, should be investigated further as a promising novel approach to cancer therapy.

Prostaglandin E2 Receptor 4 (EP4) as a Therapeutic Target to Impede Breast Cancer-Associated Angiogenesis and Lymphangiogenesis

TLDR
COX-2 is a major promoter of both events, primarily resulting from the activation of prostaglandin E receptor EP4 on tumor cells, tumor-infiltrating immune cells, and endothelial cells; and induction of oncogenic microRNAs.

EP3 receptor antagonist L798,106 reduces proliferation and migration of SK-BR-3 breast cancer cells

TLDR
Antagonism of the EP3 receptor results in a reduced proliferation and migration of SK-BR-3 breast cancer cells, potentially mediated via a Gi-protein-cAMP pathway and suggests that EP3 plays a role in tumorigenesis.

Eicosanoids in Cancer: New Roles in Immunoregulation

TLDR
The existence of small molecular inhibitors and activators of eicosanoid pathways such as specific receptor blockers make them attractive candidates for therapeutic trials, especially in combination with novel immunotherapies such as immune checkpoint inhibitors.

EP4 as a Therapeutic Target to Impede Breast Cancer-associated Angiogenesis and Lymphangiogenesis

TLDR
It is shown that COX-2 is a major promoter of both events, primarily resulting from the activation of Prostaglandin E receptor EP4 on tumor cells, tumor-infiltrating immune cells, and endothelial cells; and induction of oncogenic microRNAs.

Eicosanoid regulation of debris-stimulated metastasis

TLDR
It is shown that the synergistic antitumor activity of sEH and EP4 inhibition suppresses hepato-pancreatic tumor growth, without overt toxicity, via macrophage phagocytosis of debris and counterregulation of a debris-stimulated cytokine storm.

COX-2-PGE2-EPs in gynecological cancers

TLDR
An overview of the current knowledge of COX-2-PGE2-EPs signaling in endometrial cancer, ovarian cancer and cervical cancer is provided and EPs represent promising anti-inflammation biomarkers for gynecological cancer and may be novel treatment targets in the near future.

Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro

TLDR
A new combination regimen of photodynamic priming (PDP) and prostaglandin E2 receptor 4 (EP4) inhibition that reduces the migration and invasion of two human ovarian cancer cell lines in vitro.

Characterization of miR-574-5p decoy to CUGBP1 in human lung cancer cells using a mass spectrometry proteomics approach

TLDR
A proteomics approach was conducted in order to gather global insights into the proteome changes related to miR-574-5p and CUGBP1, especially in a compartment specific manner and it is assumable that this novel decoy mechanism is specifically regulating mPGES-1 in A549 lung cancer cells.

Targeted eicosanoids profiling reveals a prostaglandin reprogramming in breast Cancer by microRNA-155

TLDR
The data suggest an alternative way for suppressing PGE2 production via the inhibition of miR-155, which significantly correlates with breast cancer patients’ survival.

References

SHOWING 1-10 OF 106 REFERENCES

G protein-coupled receptors as promising cancer targets.

Prostaglandin E2 EP receptors as therapeutic targets in breast cancer

TLDR
While preclinical and epidemiological data support the use of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors (COXibs) for the prevention and treatment of malignancy, toxicities due to COXIBs as well as less than promising results from clinical trials have laboratories seeking alternative targets.

G protein-coupled receptors: novel targets for drug discovery in cancer

TLDR
This work reviews recent findings that present unexpected opportunities to interfere with major tumorigenic signals by manipulating GPCR-mediated pathways and discusses current data regarding novel G PCR targets that may provide promising opportunities for drug discovery in cancer prevention and treatment.

Prostaglandin E receptor EP4 is a therapeutic target in breast cancer cells with stem-like properties

TLDR
These studies support the continued investigation of EP4 as a potential therapeutic target and provide new insight regarding the role ofEP4 in supporting a breast cancer stem cell/tumor-initiating phenotype.

E-type prostanoid receptor 4 (EP4) in disease and therapy

Role of β-arrestin 1 in the metastatic progression of colorectal cancer

TLDR
The results show that the prostaglandin E/β-arrestin 1/c-Src signaling complex is a crucial step in PGE2-mediated transactivation of the EGFR and may play a pivotal role in tumor metastasis.

Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets?

TLDR
This review focuses on PGE2, and in particular on the role of the individual EP receptors and their signalling pathways in neoplastic disease, and the potential for exploiting the EP receptors as therapeutic targets for the treatment of cancer and metastatic disease.

Prostanoid receptors: subtypes and signaling.

TLDR
Alternative splice variants described that alter the coding sequence in the C-terminal intracellular tail region modulate signal transduction, phosphorylation, and desensitization of these receptors, as well as altering agonist-independent constitutive activity.
...